Large Study Reveals Long-Term Outcomes for Prostate Cancer Patients Treated with High Dose, Short Term Radiation like CyberKnife Radiotherapy

WASHINGTON –– A large, national study examining a radiation treatment for prostate cancer––popular because it delivers a high dose of therapy in a very short time frame––supports its routine use. 

The study, conducted at cancer centers around the United States including at Georgetown Lombardi Comprehensive Cancer Center, looks at long term follow up data for stereotactic body radiotherapy (SBRT) used to treat more than 2,100 men with prostate cancer that had a low or intermediate risk of recurring.

The results were published Feb. 8 in the journal JAMA Network Open.

At MedStar Georgetown University Hospital, the therapy is delivered by a system called CyberKnife, which delivers high doses of radiation precisely aimed to minimize the involvement of healthy surrounding tissue.

Radiation oncologist Sean P. Collins, MD, PhD, says curative treatment is a shared goal along with maintaining a person’s quality of life.  Side effects, including impotence, can occur with all treatments for prostate cancer and can happen years after treatment.

“While it is necessary to observe these men for decades, our interim seven-year data show that survival and side effects are comparable to other forms of radiotherapy,” says Collins, director of the CyberKnife Prostate Program at MedStar Georgetown University Hospital and an associate professor of radiation medicine at Georgetown University. 

The National Comprehensive Cancer Network, which establishes cancer treatment guidelines, classified SBRT as an alternative to conventional therapy, but had noted a lack of long term follow up data. There is much more experience with conventionally fractionated radiation therapy, delivered five times a week for up to nine weeks, and brachytherapy, in which radioactive seeds are implanted in the prostate.

“Our findings give us great confidence that CyberKnife should become a standard option for some men who want to avoid the hassle and inconvenience of standard therapy,” Collins says.

 

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Collins reports receiving grants from and being a paid consultant for Accuray Inc., the maker of CyberKnife.

 

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Prostate Cancer Patient Does His Research and Chooses Proton Therapy to Treat His Aggressive Disease

Dr.-Lischalk-with-Denwiddie(Washington, D.C.)  When Melvin Denwiddie, 73 was diagnosed with prostate cancer in late 2016 his physicians first told him the “watch and wait” strategy would be sufficient.  But in 2017 further testing showed that his cancer had become more aggressive and it was time to get treated.

“My prostate cancer was potentially fatal if I didn’t start treatment,” says Denwiddie. “My choices were surgery to remove the prostate, traditional radiation or proton radiation,” says the great-grandfather of three. “I did my research and I wanted proton therapy.  I found that proton therapy would be the most accurate; it would follow the shape of my tumor and would penetrate only the tumor and not any of the tissue outside of the tumor.  That was very important to me.”

That’s when he found proton therapy at MedStar Georgetown University Hospital and his radiation oncologist, Jonathan Lischalk, MD.

“It’s important to sit down with patients and discuss their treatment options,” says Dr. Lischalk. “For localized prostate cancer, a variety of treatment options exist including surgery and radiation therapy.  Even within radiation therapy, many options exist including proton therapy, x-ray-based therapy, and brachytherapy.  Helping a patient understand his treatment options, the related side effects, and the clinical outcomes is extremely important.”

The proton therapy system at MedStar Georgetown is the first and only in the Washington, D.C. metropolitan area and is the first in the world to offer proton therapy with HYPERSCAN™ technology. HYPERSCAN produces beams that are sharper than other proton systems and treats patients faster.

Denwiddie received 43 proton treatments over the course of July through September 2018.

“From my standpoint, proton therapy is a very good treatment process. It was not invasive, it wasn’t painful and I experienced very few side effects,” says Denwiddie.  “Aside from my bladder becoming overactive, it was a pretty easy treatment from beginning to end.  And any side effects I had are getting better.”

With proton therapy complete, Denwiddie continues with hormone treatments for his prostate cancer under the care of his urology team at MedStar Georgetown.

Denwiddie with Dr. Lischalk in an exam room
Melvin Denwiddie (left) and Dr. Lischalk (right)

“Proton therapy is proving to be an excellent option for prostate cancer treatment,” say Ryan Hankins, MD, a urologist at MedStar Georgetown University Hospital. “From a urology standpoint, I am able to use a small needle through the skin to place the needed fiducial markers and gel spacer to help improve patient outcomes and make proton therapy more precise. This is done with no incisions on the skin. Dr. Lischalk and I also coordinate patient visits to help make the patient's visit to MedStar Georgetown as seamless as possible.”

Denwiddie is a retired accountant for NASA but continues to prepare tax returns and represent clients before the Internal Revenue Service. “It’s a labor of love I’ve been practicing since 1972.  It’s such a pleasure to know that I can continue to help people when they need it in this way.”

With his wife of more than 50 years newly retired and his prostate cancer treated, Denwiddie looks to the future with optimism and excitement.

“I feel confident that this prostate cancer is a thing of the past. The rest of my life, I’m looking forward to enjoying the freedom and flexibility to move around and travel with my wife.  That includes visiting family and places I haven’t had the opportunity to see yet. I’m very excited about my future.”

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For Some Bladder Cancer Patients, Simple Test Could Reduce Over-Treatment, Ease High Cost

WASHINGTON — Bladder cancer is relatively common and imposes the highest per patient cost on the U.S. health care system than the management of any other cancer type. Now, a new test could be key to reducing the cost of care while at the same time, relieving some patients of unneeded over-treatment, say investigators led by Georgetown Lombardi Comprehensive Cancer Center researchers.

Deciding whether to treat bladder cancer aggressively has been difficult — predictive diagnostic data is limited.  Up to 70 percent of patients treated for early stage lesions that have not invaded the bladder wall will experience recurrence of these lesions, and 20 percent of these patients will develop an invasive cancer. 

Because clinicians do not know which tumors will become dangerous, they err on the side of caution and perform an extremely intensive post-surgery surveillance regimen, including cystoscopy (a lighted optical scope that examines the inside of the bladder) as frequently as every three months for two years after removal of the tumor, and every 6-12 months for the years after.

The Georgetown-led investigators offer a new solution to the dilemma. They have found that a fairly simple test that significantly improves the identification of bladder tumors that will likely become invasive.

The study, published in Clinical Cancer Research, “validates this test that helps predict whether an early stage bladder cancer will recur and progress,” says the study’s senior author, Todd Waldman, MD, PhD, a professor of oncology at Georgetown.

Working with researchers from the U.S. and Denmark, Waldman has found that, compared with using current diagnostic procedures, the new test is 2.4 times more accurate in identifying tumors likely to recur after treatment, and 1.9 times more accurate at predicting which tumors will likely to progress, invade the bladder wall and spread.

The test involves examining bladder tumors that had been removed during initial surgery for over expression of the STAG2 gene, which Waldman earlier identified as key to development of potentially deadly bladder tumors.

Checking for STAG2 is a “very simple and very robust” procedure for pathologists who routinely examine excised tumors, Waldman says. His studies have described how to run this test.

Using the test could, in some cases, spare patients constant surveillance and, in others, support forgoing aggressive treatment that can produce significant side effects, the researchers say.

So Waldman and his colleagues have worked on a diagnostic test for years. This study summed up several of those clinical studies, concluding that using the test “offers additional two-fold predictive discrimination,” Waldman says.

“We are closer to our goal of lowering the risk of both aggressive bladder cancer and over-surveillance and treatment side effects in bladder cancer patients,” he says. “In principle, it might be possible to reduce the frequency of post-resection surveillance and therapy in patients whose cancer is STAG2-negative, and, conversely, treat patients and keep up high frequency surveillance in patients who have positive test results.”

The study’s first author is Alana Lelo, an MD/PhD candidate at Georgetown University School of Medicine.  Additional Georgetown authors include Deborah L. Berry, PhD, Brent Harris, MD, PhD, George Philips, MD, Krysta Chaldekas, and Jung-Sik Kim, PhD. Frederik Prip, Lars Dyrskjøt, PhD, Jørgen Bjerggaard Jensen, MD, are from Aarhus University Hospital, Denmark; Jeffry Simko, MD, PhD, and David Solomon, MD, PhD, are from the University of California San Francisco School of Medicine; Ciaran Mannion, MD, and Pritish Bhattacharyya, MD, are from Hackensack University Medical Center, New Jersey, and Anagha Kumar, MD, is from MedStar Health Research Institute in Washington D.C.

The authors declare no potential conflicts of interest.

This work was supported by the National Cancer Institute grants (R01CA169345, T32CA009686, DP5OD021403), and Cancer Center Support Grant (P30CA051008) to the Histopathology and Tissue Shared Resource); the Danish Cancer Society; the National Center For Advancing Translational Sciences of the National Institutes of Health (TL1TR001431); and institutional funds from the John Theurer Cancer Center at Hackensack University Medical Center.

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Women Replacing Breast Implants with Their Own Tissue, a Growing Trend

(Washington, D.C.) – When Cynthia Davis of Virginia was diagnosed with breast cancer in 2015 she elected a double mastectomy with implants.  Before her surgery she had chemo therapy.  Radiation followed.

As she recovered and went back to her active and athletic lifestyle that included bicycling, yoga and weight lifting, Davis noticed that she was experiencing pain and irritation associated with her implants.   

“The more active you are the more you use your chest wall,” says Davis now age 60.  “If you’re not doing anything it doesn’t bother you, but I went back to bike riding, the gym and yoga and the more I did, the more it bothered me.”

Cindi-Davis-with-paddle

In 2017, Davis saw an opportunity to try a new sport. Having rowed years earlier, she knew she enjoyed water sports. Last summer, she found and joined “GoPink!DC”  - a dragon boat team made up of breast cancer survivors and supporters.

“The more I paddled with the team, the more uncomfortable my chest became.  I realized that if I wanted to continue being active and do well on this team, I was going to have to do something about the implants.”

Davis also noticed that cosmetically, because the implants were placed under her chest wall muscles that her breasts appeared to flex and there were certain yoga poses that were not possible because of her implants.

“A large part of my practice is fixing previous reconstructions with breast implants and replacing them with a woman’s own tissue,” says David H. Song, MD, Physician Executive Director of Plastic Surgery for MedStar Health and Chairman of Plastic Surgery at MedStar Georgetown University Hospital.

Davis went to see Dr. Song at MedStar Georgetown where he recommended a procedure that would replace her implants with her own tissue and make her more comfortable. The procedure Dr. Song recommended is called DIEP flap in which blood vessels called deep inferior epigastric perforators, as well as the skin and fat connected to them are removed from the lower abdomen and transplanted into the chest.

Dragon-Boat-teamDavis had the surgery in March of 2018.

“I’m thrilled,” says Davis.

“I woke up in recovery with the implants gone and when they asked me what my pain number was, I almost cried because I realized the pain in my chest was gone. Even with the stitches the pain was gone. I traded in my implants for a double DIEP.”

Davis had the surgery on a Wednesday and went home from the hospital four days later.

The DIEP flap procedure is performed using a surface incision from hip to hip.  Dr. Song says the use of a non-opioid pain medication called Exparel™ has been a “game changer.” 

“I believe that more than 90 percent of women needing breast reconstruction are candidates for a tissue-based procedure,” says Dr. Song.  “I can take tissue from the tummy, thigh, buttocks or back. In the case of a DIEP flap, patients get a tummy tuck and a breast reconstruction at the same time.”

In addition to DIEP flap, there are as many as 4 additional procedures that Dr. Song performs that use a woman’s own tissue for reconstruction.

(Video courtesy of Robin Barr)

Radiation therapy for breast cancer after reconstruction with implants is associated with complications. 

“Radiated implants put women at greater risk of pain, discomfort, hardened breasts and even ruptured implants,” says Dr. Song. “With radiation, the success rate for implants after five years is only about 65 percent.  The life span of implants is 10-14 years; when using your own tissue, once you’re done, you’re done.”

“I’m back to paddling with GoPink!DC twice a week,” says Davis.  “By the end of the summer I will be racing, and I’ll be pain free.”

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MedStar Georgetown First and Only Center in the Washington, D.C. Metropolitan Region to Offer Proton Therapy for Cancer Patients

Dr. Brain Collins with MedStar Georgetown’s first patient to receive proton therapy.(Washington, D.C) April 17, 2018- For the first time, cancer patients in the Washington, D.C. metropolitan region have access to the latest cancer-fighting technology, proton radiation therapy, now available at the MedStar Georgetown University Hospital Proton Therapy Center.

Martha Ramos, 53 of Maryland became MedStar Georgetown’s first patient to receive proton therapy.  Ramos is being treated for recurrence of a brain tumor.  

“It’s encouraging to know that this kind of radiation will result in less damage to the healthy area of my brain,” says Ramos. 

Proton therapy is more precise and targeted than conventional radiation. It works by using pencil beam scanning, similar to a 3D printer, to match the tumor’s exact shape and size with superior accuracy that eliminates the exit dose of traditional radiation, and spares healthy tissue.

MedStar Georgetown is the first and only proton center in the world to offer the Mevion S250i with HYPERSCAN™ technology, producing beams that are sharper than previous proton systems. Proton therapy with HYPERSCAN is also faster than other proton systems, benefiting patients whose treatment includes holding their breath.

“I am extremely excited to be able to offer this latest advancement, proton therapy, to my patients,” says Brian Collins, MD, a radiation oncologist and clinical director of the new proton therapy center.  “It’s clear that this treatment will help to improve the clinical outcomes for our cancer patients and decrease their side effects when radiation is needed.”

 “In certain cases, proton therapy can be a game changer,” says Keith Unger, MD, radiation oncologist at MedStar Georgetown.  “It allows us to treat cancers where traditional radiation might not even be possible."

How Protons Destroy Cancer

“Proton therapy is an advanced form of radiation that can destroy cancer cells,” says Peter Ahn, MD, a radiation oncologist at MedStar Georgetown.  “A machine called a cyclotron speeds up protons to two thirds the speed of light and they become highly charged.  These high energy protons are then delivered to the tumor as an invisible beam that eradicates the cancer.  Because we can more tightly control the protons than we are able with traditional radiation, proton therapy can be given without damaging critical tissues and structures near the tumor because the beam conforms  precisely to the tumor’s size and shape, sparing healthy tissue.”

Advantages of HYPERSCAN™

HYPERSCAN is an FDA-approved proprietary technology that has advantages over existing proton therapy systems. In addition to producing a micro beam that is sharper than many current proton systems and reducing damage to nearby healthy tissue, HYPERSCAN is also faster than other pencil beam scanning systems which can reduce the margin of error in treating tumors that are affected by breathing or organ motion.  This improves both treatment accuracy and patient comfort as patients need to spend less time lying still.

“HYPERSCAN is currently the most precise type of proton therapy in the world,” says Dr. Ahn. 

“Proton therapy with HYPERSCAN can be given from head to toe,” says Dr. Collins.

Cancer Treatment for Patients with Fewer Side Effects

Proton therapy is beneficial for pediatric cancer patients because it lowers their exposure to radiation avoiding unnecessary exposure to healthy tissue and resulting in less growth impairment as they grow up.  Children are less likely to develop a secondary cancer later in life when treated with proton therapy as it treats tumors while keeping health surrounding tissues unharmed.

proton therapy patient with doctorProton therapy is also effective in treating re-current tumors.

 “There are also certain types of cancer where you have to deliver a very high dose of radiation right next to a critical structure like the spinal cord or brainstem,” says Sonali Rudra, MD, radiation oncologist at MedStar Georgetown. “With proton therapy we can deliver a high dose to the area we are trying to target and minimize the radiation beyond the tumor.  So for some patients, proton therapy might be their only radiation treatment option.”

“Proton therapy can also be a good option for patients with left-sided breast cancer, which is close to the heart,” says Dr. Rudra. “When indicated for breast cancer, using proton therapy instead of traditional radiation means more control over the radiation itself and less potential damage to the heart and lungs.”

Proton Therapy Closer to Home and Under One Roof

“The addition of proton therapy is a logical next step for a center like MedStar Georgetown as part of the Lombardi Comprehensive Cancer Center, dedicated to and recognized for providing the latest cancer treatments and access to clinical research trials,” says Dr. Collins.

Lombardi Comprehensive Cancer Center is one of only 49 sites in the nation and the only center in Washington, D.C. to earn the prestigious Comprehensive Cancer Center designation by the National Cancer Institute.

“All the multiple specialties and disciplines involved in cancer care are here helping to support patients through their treatment, in one location, under one roof,” says Dr. Unger. “They no longer have to travel outside of our area to receive this advanced treatment.”

 “The addition of proton therapy means MedStar Georgetown offers the full range of radiation treatments for cancer that are available,” says Dr. Collins.  “For patients that means we take an individual approach when considering radiation therapy. Whether it’s CyberKnife, proton therapy or conventional radiation, we will choose the optimal treatment to achieve the best outcomes with the fewest side effects.”

 

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Family History Increases Breast Cancer Risk Even in Older Women: Weighing Screening Options

WASHINGTON Family history of breast cancer continues to significantly increase chances of developing invasive breast tumors in aging women — those ages 65­ and older, according to research published in JAMA Internal Medicine. The findings could impact mammography screening decisions later in life.

The large study of more than 400,000 women is the first to specifically look at family history as a breast cancer risk factor in two groups of women, age 65-74 and 75 and older, says the research team, led by Dejana Braithwaite, PhD, associate professor of oncology at Georgetown University School of Medicine and a member of Georgetown Lombardi Comprehensive Cancer Center.

“Family history of breast cancer does not decline as a breast cancer risk factor as a woman ages. The relationship didn’t vary based on whether a first-degree relative’s diagnosis was made in a woman age 50 or younger, or older than age 50,” Braithwaite says. “This means that women with that first-degree family history — breast cancer in a mother, sister, or daughter — should consider this risk factor when deciding whether to continue mammography screening as they age.”

Currently, the U.S. Preventive Services Task Force (USPSTF) recommends mammography screening every two years between ages 50 and 74 for women at average risk. After age 75, the evidence is insufficient to assess risk and benefit of mammography, according to USPSTF’s most recent update in 2016.

The American Cancer Society recommends yearly mammograms in women age 45, and then biennial screening at age 55 and on “as long as a woman is in good health.”

“As breast cancer screening guidelines change from age-based to risk-based, it is important to know how standard risk factors impact breast cancer risk for women of different ages,” said Karla Kerlikowske, MD, senior author of the new study and a member of the UC San Francisco Helen Diller Family Comprehensive Cancer Center.

“The goal of our work is to provide evidence that helps inform breast cancer screening guidelines for older women,” Braithwaite says. “Older women who are in good health and have a first-degree family history may consider a screening mammogram even as they age beyond the screening recommendations for average risk women.”

Researchers from Washington, California, Wisconsin, Vermont, New Hampshire and North Carolina participated in the research by examining 1996-2012 records from the Breast Cancer Surveillance Consortiums (BCSC) registries in their regions.

The team found that while age is the strongest risk factor for breast cancer — any adult woman in the general population has a baseline 12 percent risk of developing the disease — first-degree family history can almost double that risk.

Overall, a first-degree family history leads to an absolute increase in 5-year risk of breast cancer ranging from 1.2 to 10.3 percentage points depending on breast density and age. For example, in women 65-74 years old with scattered areas of dense tissue in their breasts, the team found an increased 5-year risk of breast cancer that ranged from 15.1 percent in women without a family history of the disease to 23.8 percent in women whose first degree female relatives had developed breast cancer.

Similarly, among women 75 years or older with the same scattered breast density, 5-year cumulative risk of breast cancer increased from 15.9 percent for women without a family history to 23.1 percent for women with a family history.

Researchers also discovered that breast density, one of the strongest risk factors for breast cancer, did not attenuate the association of family history of breast cancer and breast cancer risk in the women studied as a whole. But when broken into age groups, fatty breasts added a little risk to women age 65-74 years with a family history; in the older cohort, the association was flipped — dense breasts added slight risk.

Study co-authors include: Diana L. Miglioretti, PhD, from the University of California, Davis; Weiwei Zhu, MS, and Diana S. M. Buist, PhD, Kaiser Permanente Washington Health Research Institute in Seattle; Joshua Demb, MPH, Elad Ziv, MD, Jeffrey A. Tice, MD, and Louise C. Walter, MD, of the University of California, San Francisco; Amy Trentham-Dietz, PhD,   of the University of Wisconsin at Madison; Brian Sprague, PhD of the University of Vermont College of Medicine;  Tracy Onega, PhD, of Dartmouth; and Louise M. Henderson, PhD, of the University of North Carolina, Chapel Hill.

The authors report having no personal financial interests related to the study.

This work was supported by a National Institutes of Health, National Cancer Institute–funded Program Projects (P01 CA154292, 1R01CA207361-01A1). Data collection was additionally supported by the Breast Cancer Surveillance Consortium (HHSN261201100031C).

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The Day of Dance at MedStar Georgetown

2017 MGUH Day of DanceMedStar Georgetown recently hosted the “Day of Dance” which brought healing music and movement to patients, visitors and associates alike.

2017 MGUH Day of Dance ViolinistBeginning in the Lombardi atrium, passersby heard and saw something unusual: violin music reverberated through the lobby as dancers moved to the rhythm of the music. Dressed in soft grey and white tones, 12 dancers moved in sync with the goal of infusing open spaces in the Hospital with lightness and joy. Anthony Hyatt, the violinist, kept a peaceful, yet playful tempo and engaged everyone as the dancers (or movement choir) slowly and gracefully made their way from the atrium to other parts of the Hospital, including hematology/oncology infusion centers.

The movement choir and musical accompaniment are a part of an ongoing initiative to bring the healing arts to MedStar Georgetown. “We believe movement is a part of health,” says Julia Langley, faculty director of the Arts and Humanities Program for the Lombardi Comprehensive Cancer Center. “Integrating arts into the Hospital helps patients and their loved ones see that beauty is around them and they can take part in it.”

Qualitative studies show that music is beneficial to the practice of medicine. “The arts are a way to help patients heal from the inside out,” Langley says. “It’s a creative and constructive response to illness. If we can study arts like science studies medicine, we’ll be doing good in the name of cura personalis.” The Day of Dance at MedStar Georgetown is just one way that the Arts and Humanities Program aims to care for the whole person.

2017 MGUH day of Dance

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MedStar Health Taps Louis M. Weiner, MD, to Lead MedStar Georgetown Cancer Institute

WASHINGTON -- MedStar Health, the largest not-for-profit healthcare system across Maryland and the Washington, D.C., region, has named Louis M. Weiner, MD, as director of its MedStar Georgetown Cancer Institute.  Weiner will serve in this capacity while also remaining director of Georgetown Lombardi Comprehensive Cancer Center, Washington’s only National Cancer Institute (NCI)-designated Comprehensive Cancer Center and the research engine of the institute.

Dr. Louis M. WeinerAs director of the MedStar Georgetown Cancer Institute, Weiner will lead the development and coordination of clinical care and research programs spanning prevention, treatment, rehabilitation, survivorship and end-of-life care across the MedStar Health system.

"I am honored to have the opportunity to lead this effort,” says Weiner. “This is an exciting time for the field of cancer therapy, as new treatments are transforming the outlook for patients with this dreaded set of diseases. The MedStar Georgetown Cancer Institute links our nationally renowned cancer specialists across the Washington metropolitan region to offer the highest possible level of research-inspired cancer care, always maintaining the focus on the well-being of the patient. The Institute's alignment with the Georgetown Lombardi, one of the nation's National Cancer Institute-designated Comprehensive Cancer Centers, assures that our patients will always receive tomorrow's treatments today."

An internationally recognized medical oncologist specializing in the treatment of gastrointestinal cancers, Weiner is an accomplished researcher who focuses on monoclonal antibody research and other immunotherapy treatments. He serves as chair of the NCI’s Board of Scientific Counselors and as a member of its Clinical Trials Advisory Committee. In addition, Weiner recently concluded service as a member of the Advisory Panel of the National Institutes of Health (NIH) Center for Scientific Research, which administers NIH research grants. Lou earned his bachelor’s degree in biology from the University of Pennsylvania and his medical degree from Mount Sinai School of Medicine. He completed his fellowship at Tufts University School of Medicine. Prior to his appointment as Georgetown Lombardi director in 2007, Weiner held several leadership positions at Fox Chase Cancer Center in Philadelphia.

The integration of MedStar Health’s clinical care and Georgetown Lombardi’s robust research platform will bring advanced cancer care, greater access to clinical trials and state-of-the-art technologies to patients at more convenient locations.  It is a direct outgrowth of the continuing collaborations of Georgetown University and MedStar Health, reflected by a recent agreement to extend and enrich existing interactions between the two enterprises.

“Weiner is uniquely qualified to lead this effort with expertise as a clinician, clinical researcher, laboratory scientist, director of a large research operation and experience in service delivery,” says M. Joy Drass, MD, Executive Vice President and Chief Operating Officer of MedStar Health.

“This important collaboration amplifies our shared commitment to the health and wellness of the communities we serve by further elevating the level of cancer services and research-inspired cancer care now available to all of our patients,” says Edward B. Healton, MD, MPH, executive vice president for health sciences at Georgetown University Medical Center and executive dean of the Georgetown School of Medicine.

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Two Agents Deliver Knockout Punches to Ewing Sarcoma

WASHINGTON When combined with an already FDA-approved chemotherapy, a novel agent developed by researchers at Georgetown Lombardi Comprehensive Cancer Center, appears to halt the ability of Ewing sarcoma to grow and progress.

The finding, in cell lines and animal models, warrants clinical investigation to see if the combination would be an effective treatment as well as a less toxic alternative to current therapy for the rare bone cancer, the researchers say.

The study, published October 3 in the journal Science Signaling (Inhibition of the oncogenic fusion protein EWS-FLI1 AQ1 causes G2-M cell cycle arrest and enhanced vincristine sensitivity in Ewing’s sarcoma), tests a combination of YK-4-279, the compound developed at Georgetown, with vincristine in laboratory and mice studies. Vincristine is one of the chemotherapy drugs now used to treat Ewing sarcoma.  

“Each of the two drugs impacts the cancer cell’s ability to survive, but they do it in a way that magnifies their effectiveness compared to if they were used alone. It’s like a left hook followed by an uppercut,” says the study’s senior investigator, Jeffrey Toretsky, MD, the new chief of Pediatric Hematology Oncology at MedStar Georgetown University Hospital, and researcher at Georgetown Lombardi.

In the United States, about 500 children and young adults are diagnosed with Ewing sarcoma annually. Between 60 to 70 percent of patients survive more than five years, but with many late effects from treatment. Patients with Ewing sarcoma are currently treated with a combination of five different chemotherapy drugs, which often damages nerves and few treatments lead to a cure when the cancer progresses, Toretsky says.

Ewing sarcoma is caused by the exchange of DNA between two chromosomes. The resulting EWSR1-FLI1 gene produces a fusion protein, EWS-FLI1, responsible for cancer’s growth. In 2006, Toretsky and his team discovered that the fusion protein binds to another protein, RNA helicase A (RHA), which is important for cancer progression.

YK-4-279 directly inhibits EWS-FLI1. Toretsky’s work on YK-4-279 led to the eventual development of TK216, a first-in-class small molecule that is now being studied by Oncternal Therapeutics in a clinical trial in patients with relapsed or refractory Ewing sarcoma.

In this study, Toretsky led a team of researchers that tested 69 different anti-cancer drugs to find an agent that would work synergistically with YK-4-279. They discovered that together, the drugs produce a “microtubule catastrophe” in Ewing sarcoma cancer cells.

Microtubules are tube-like structures that help cells keep their shape and act like highways that transport cellular proteins. They also pull apart chromosomes when they divide, and it is this action that is particularly affected by the drug combo, Toretsky says.

“Cancer needs to grow, and to do that, the cells need to divide and multiply. This is the step both drugs target, but in different ways,” he says.

According to Toretsky, Oncternal is planning to test the combination of TK216 and vincristine in patients.

Co-authors include Georgetown researchers Stefan K. Zöllnerm MD (the study lead author), Saravana P. Selvanathan, PhD, Garrett T. Graham, PhD, Ryan M. T. Commins, MD, Sung Hyeok Hong, DVM, PhD, research fellow Eric Moseley, college student Sydney Parks, medical student Jessica N. Haladyna, Hayriye V. Erkizan, PhD, and Aykut Üren, PhD; Uta Dirksen, MD, from the Essen University Hospital, Germany; and Michael D. Hogarty, MD, from the Children’s Hospital of Philadelphia.

The Georgetown researchers are funded by the Children’s Cancer Foundation, Nick Currey Fund, St. Baldrick’s Foundation, Alan B. Slifka Foundation, CureSearch, Go4theGoal, Liddy Shiver Sarcoma Initiative, as well as a Burroughs Wellcome Clinical Scientist Award in Translational Research and the NIH (RC4CA156509, RO1CA133662, and R01CA138212).

Georgetown University owns the underlying YK-4-279 technology and related intellectual property invented by Toretsky, Üren, et al., and has licensed the technology to Oncternal for development as a potential therapeutic agent for cancer, including Ewing sarcoma. Toretsky is a paid scientific advisor to Oncternal.                                           

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Transferring Lymph Nodes from One Part of the Body to Another to Treat Lymphedema

Susan with her childrenSusan Wolfe, 51 of northern Wisconsin is enjoying relief from the debilitating side effects of breast cancer surgery and radiation thanks to a revolutionary procedure now available at MedStar Georgetown that allows surgeons to transfer lymph nodes from one part of the body to another.

Susan was diagnosed with stage III B breast cancer in August 2011 after what she thought was just a cyst that kept getting bigger.

“I sat my kids down and told them ‘we’re going to laugh our way through this and get through it one way or another.’ As a single mom who had just lost my full-time day job, I was determined to keep going with my education and my treatment,” says Susan.

Working as a waitress and newly enrolled in General Business classes pursuing her Associates Degree, Susan worked all the way through her surgery, chemotherapy and 33 rounds of radiation.

After graduation from her program in 2012, Susan had six surgeries to try to reconstruct her breast to relieve the tissue and scar damage that was left behind due to radiation.

“Because 18 lymph nodes were removed during my mastectomy, then the radiation and because the tumor had been the size of a lime and so deep in my chest wall, the skin of my left arm and chest got so uncomfortably tight.”

Susan began to experience a condition called lymphedema, a painful and disfiguring side effect of breast cancer surgery that removes the lymph nodes and radiation that can damage healthy tissue.

“My arm ached terribly,” says Susan.  “It was always so heavy. Due to the radiation and surgeries, the tissue from my shoulder to my chest was stretched as tight as you can imagine.”

 “The lymph nodes are responsible for clearing the body of wastes, bacteria and other substances from tissues,” says David H. Song, MD, Washington Regional Chief of Plastic Surgery for MedStar Health and chief of Plastic Surgery at MedStar Georgetown University Hospital.  Dr. Song is an internationally recognized expert in plastic surgery and is known for his pioneering work in lymphovenous bypass and lymph node transfer using microsurgical and super-microsurgical techniques to reduce the severity of lymphedema.

“When you remove the lymph nodes for breast cancer surgery or the area undergoes radiation to treat the cancer, a condition called lymphedema can occur in up to 20 percent of women, says Dr. Song.”

“It was terrible.  Despite physical therapy, lymphatic massage, using a compression pump daily and wearing my compression sleeve, I could only wear sleeveless clothes or clothing with very large sleeves,” says Susan. “I had to lie down in awkward positions, so sleeping was difficult. And the lymphedema was only getting worse.”

Susan with her 2 sistersSusan was referred by her oncologist to the University of Chicago Medical Clinic for lymph node transfer where she met with Dr. Song in 2016 when he worked in Chicago.  At the time, Dr. Song was in the process of coming to MedStar Georgetown University Hospital.  Then in May 2017 Susan came to Georgetown for a new procedure where Dr. Song would remove healthy lymph nodes from her back and side and transfer them to the affected area around her left breast.

“By adding in lymph nodes, it restores the arm to start draining lymph again,” says Dr. Song.  “Akin to small pumps that grow new lymph channels to drain fluid and return tissue to normal size. “

“It was amazing,” says Susan. "After the surgery I had immediate relief. And I mean immediate. That heavy aching feeling was gone.”

Patients can usually leave the hospital in a few days and get back to some of their activities in a week or two.

“I had the surgery on a Tuesday, was on a work conference call on Thursday and back at work the following Tuesday.”

Dr. Song says lymph node transfer isn’t for everyone. “Patients with severe skin changes and thickening are not good candidates for lymph node transfer but we have other techniques we can offer to address problems with lymph drainage.”

“I’m so happy.  My quality of life is so much better.  You do things with your hands and arms that you don’t even realize. Walking with my arm down made it swell up.  I can wear regular clothing again. This procedure has changed so many things for me.”

Now working as a general manager for a large hospitality chain, Susan wants other women to know that there is life and love after cancer.

"I was blessed to remarry four years to the date of my last chemotherapy treatment, a very special day indeed! I wore the pink breast cancer shoes for my wedding, took them off and handed them to my husband before the ceremony and said, ‘I'm officially handing over my running shoes.’"

Susan with her husband and pink breast cancer shoes

Media Contact

Marianne Worley
Director of Media Relations
Office: 703-558-1287
Pager: 202-405-2824
[email protected]

 

Request an Appointment

To learn more about lymphedema treatment at MedStar Georgetown, visit MedStarGeorgetown.org/Lymphedema or call 855-482-6671 to make an appointment. 

 

Meet Dr. Song

Dr. Song is the Washington Regional Chief of Plastic Surgery for MedStar Health and chief of Plastic Surgery at MedStar Georgetown University Hospital. Watch Dr. Song discuss reconstructive plastic surgery.