Cancer Update May 2016

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Issue No. 33 IN TH I S I SSU E 6 BREAST CANCER: Taking aim at aggressive cancer 8 TEAMWORK: First commercial blood test for lung cancer 10 REVOLUTIONARY: New brain cancer treatment

The Gynecologic Oncology Division at the Helen F. Graham Cancer Center & Research Institute

Strong medicine for ovarian and other gynecologic cancers Drs. Stephanie Jean, Mark Cadungog and Mark Borowsky

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Mark Cadungog, M.D., directs minimally invasive, robotic surgery.

endy Bosari is a survivor. After 11 years, she is still fighting and living with ovarian cancer. Wendy is determined that this cancer will not define her or her family, those she relies on for strength and support.

That extended “family” includes the members of her cancer care team, led

by Gynecologic Oncology Division Director Mark Borowsky, M.D., at the Helen F. Graham Cancer Center & Research Institute.

“The Graham Cancer Center is a place where I really feel cared about as well as expertly cared for,” she said.

“Everyone is upbeat and positive, helpful and encouraging. When I’m there, I am Wendy, not just another patient, and that is huge.”

Through genetic testing provided by the Graham Cancer Center’s High-Risk Familial Cancer Registry and Genetic Counseling program, Wendy learned her cancer was the result of a harmful, inherited BRCA gene mutation.

Although rare, BRCA mutations increase a woman’s risk for breast, ovarian and other cancers.

Armed with that knowledge, Dr. Borowsky and his team have explored every available therapy to slow the progression of Wendy’s stage 4 ovarian cancer. She has had multiple rounds of different chemotherapy agents, including targeted molecular agents only available through the Graham Cancer Center’s participation in the National Cancer Institute (NCI) Clinical Trial Network Program.

“Unlike standard chemotherapy, this new class of drugs represents a more personalized form of medicine that targets specific biochemical pathways leading to the growth and spread of cancer,” Dr. Borowsky explained.

As one of only 34 community sites in the nation selected by the NCI as a Community Oncology Research Program (NCORP), the Graham Cancer Center offers access to state-of-the-art

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Molecular biology and targeted therapy are the future of cancer care, and we hope to see dramatic improvements for our patients on those therapies.

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M ARK BOROW SK Y, M. D.

clinical studies for patients with both early and advanced stages of disease.

Our enrollment rate is six times the national average.

“Molecular biology and targeted therapy are the future of cancer care, and we hope to see dramatic improvements for our patients on those therapies,” Dr. Borowsky added. “Some of our patients are also eligible for trials that are trying to make surgery or radiation more precise and standard chemotherapy regimens more effective.

These types of clinical trials offered here at the Graham Cancer Center are what have the greatest potential impact on patient outcomes in the near-term.”

Because her cancer has spread to other organs, Wendy has had several surgeries, including CyberKnife, Delaware’s first and only robotic radiosurgery system, to help preserve the healthy portions of her liver.

Wendy Bosari knows Mark Borowsky, M.D., and the rest of her care team at the Graham Cancer Center are beside her in her 11-year fight against ovarian cancer.

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CyberKnife is among a growing list of leading-edge technologies deployed by the Gynecologic Oncology program to treat every kind of gynecological malignancy.

precise performance “At present, about 80 percent of the surgeries we perform here are minimally invasive, with a majority of those done using robotic laparoscopic technology,” said Mark Cadungog, M.D., co-director of Robotic Surgery and a member of the Gynecologic Oncology team. “We use the da Vinci robotic surgery system for a whole range of procedures from cancer staging to radical hysterectomy.”

For patients with advanced disease or certain medical co-morbidities, precisely targeted robotic surgery may broaden treatment options.

Drs. Borowsky and Cadungog are experts in da Vinci technology, so much so that they teach other doctors how to use the system. The capability to perform less invasive, high-precision robotic surgery, translates into shorter hospital stays, less discomfort and quicker recovery for their patients.

The Gynecologic Oncology team has introduced a procedure to replace full pelvic lymph node dissection with sentinel node biopsy, guided by

da Vinci technology, to determine if gynecological cancers have spread.

Removing just a few “sentinel” lymph nodes (rather than 20-30) where cancer most likely resides may help prevent serious complications such as lymphedema, where excess fluid collects in tissue and causes swelling.

Often the best cancer medicine comes from understanding the science behind it. Through the Center for Translational Cancer Research, the Gynecologic Oncology team is collaborating with research partners at The Wistar Institute in Philadelphia on several studies related to immunity and ovarian cancer.

Blood and tissue samples from the Graham Cancer Center’s Tissue Procurement Center are helping to tease out how our bodies’ natural defense mechanisms might be enlisted to attack ovarian and other cancers. Recently, this collaboration has led to published findings that inflammation, anti-tumor immunity and the clinical outcome of cancer patients are influenced by a common genetic difference in the TLR5 gene.

Complementing this work are plans to build a bank of tissues and serums collected from women in Delaware who have ovarian cancer. Funding for the project comes from the Delaware Ovarian Cancer Foundation (see related article on page 5) to support basic laboratory research that could eventually lead to new therapies.

Leading the research project development is Stephanie Jean, M.D., director of Gynecologic Oncology Research at the Graham Cancer Center who was recruited from the University of Pennsylvania in 2015. In addition to offering patients a full range of gynecologic oncology surgery and services, Dr. Jean’s research interests include uncovering the genetic origins of both inherited and sporadic ovarian cancer using DNA sequencing.

“As we develop the biorepository of tissues from our patients with ovarian cancer, our research team will be able to use that tissue to conduct DNA sequencing and other molecular testing to look for new treatment targets,” C ONTINU ED

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she said. This information gleaned from the tumor specimens could potentially allow doctors to personalize treatment based on a tumor’s particular molecular profile.

“As technology moves forward, we can look at ways to detect ovarian cancer earlier with less invasive methods similar to a blood test or Pap test,” Dr. Jean added.

Over time, a linked database of clinical information and outcomes from women receiving ovarian cancer care will serve as an important resource for future clinical research.

In 2016, more than 22,000 women will be newly diagnosed with ovarian cancer in the U.S., and 14,000 women will die from it, more than from any other gynecological cancer.

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As technology moves forward, we can also look at ways to detect ovarian cancer earlier with less invasive methods similar to a blood test or Pap test.

“Right now there is no good screening test for ovarian cancer,” Dr. Borowsky explained. Consequently, the disease is often diagnosed at an advanced stage after it has spread beyond the ovary. “This makes ovarian cancer very

difficult to treat,” he said. “All of us, and especially Wendy and her family, want to see this disease eradicated.”

Gift from Delaware Ovarian Cancer Foundation supports new research program

Dr. Borowsky has cleared Wendy to resume chemotherapy with a powerful new agent. “When you live with cancer as long as I have, you run out of medicines to try,” she explained. “I’m always hopeful something new will turn up. I want more than anything to see my granddaughter grow, and to attend my son’s wedding this year.”

The Delaware Ovarian Cancer Foundation (DOCF) has donated $100,000 to Christiana Care to support ovarian cancer tissue research. The gift will enable the Helen F. Graham Cancer Center & Research Institute to advance its translational research program in ovarian cancer — the first such program in the state.

The Graham Cancer Center’s Gynecologic Oncology team is exploring every avenue to get her there. ¤

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team collaboration

At the Helen F. Graham Cancer Center & Research Institute, the Gynecologic Oncology team comes together to design the best treatments for patients.

HELEN F. GRAHAM CANCER CENTER & RESEARCH INSTITUTE

“Christiana Care has long offered ovarian cancer clinical trials, and with DOCF’s generous support, we can now begin important translational research on this elusive and hardto-detect cancer,” said Mark E. Borowsky, M.D., director, Division of Gynecologic Oncology at the Graham Cancer Center.

Over the next two years, led by Stephanie Jean, M.D., director of Gynecological Oncology Research, the team will build a bank of ovarian tissues and serums collected from Christiana Care patients. It will also hire a researcher to oversee the process of procuring and analyzing these samples and creating a database of clinical information — such as surgical and chemotherapy responses and cancer recurrence times — from women receiving ovarian cancer care.

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will someday lead to more effective screenings and treatments, which are so desperately needed.” This is the foundation’s first major gift to Christiana Care for research.

“The Graham Cancer Center is already deeply engaged in many areas of cancer research at our Center for Translational Cancer Research.

Now, thanks to generous support from DCOF, we will expand this work to include ovarian cancer,” said Nicholas J. Petrelli, M.D., FACS, Bank of America-endowed medical director of the Graham Cancer Center. “Our partnership with DOCF illustrates how philanthropy can drive scientific inquiry and underscores the health system’s promise to serve as expert, caring partners in our community’s health.” ¤

“Our partnership with DOCF illustrates how philanthropy can drive scientific inquiry and underscores the health system’s promise to serve as expert, caring partners in our community’s health.”

Nicholas J. Petrelli, M.D.

The bank of ovarian tissues will allow researchers to conduct tumor molecular profiling and DNA sequencing. When they can identify and understand different mutations, they then will be able to target treatments to these specific defects.

“Women across the state turn to the Graham Cancer Center for its excellent care and compassionate people,” said ovarian cancer survivor Dorianne Short, who founded DOCF in 2009.

“We are excited to help Christiana Care start ovarian cancer research that

The Delaware Ovarian Cancer Foundation presents the first half of its $100,000 gift to support translational research for bench-to-beside approaches to prevention, screenings and treatment for this challenging form of cancer. Left to right: From the Helen F. Graham Cancer Center & Research Institute are Nicholas J. Petrelli, M.D., Bank of America endowed medical director; Mark E. Borowsky, M.D., director, division of gynecologic oncology; and Stephanie Jean, M.D., director of gynecologic oncology research.

Representing the DOCF are Survivor Liaison Carol Mesmer; Founder and President Dorianne Short; and Treasurer William Short. Ms. Mesmer and Ms. Short are survivors of ovarian cancer.

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Cancer researchers at the Helen F. Graham Cancer Center & Research Institute are taking aim at a highly aggressive form of breast cancer affecting women in Delaware more so than anywhere else in the nation.

Targeting Aggressive Breast Cancer

A report published last spring in the Journal of the National Cancer Institute ranked Delaware higher than any other state for the incidence of what is known as triple negative breast cancer (TNBC).

Delaware’s experience supports national findings that African-American woman have twice the risk for TNBC as Caucasian women. Data from the Graham Cancer Center also shows that despite aggressive screening efforts and similar rates of mammograms, more than one quarter of the AfricanAmerican women diagnosed during an eight-year period had late stage or advanced disease; this was true for only 15 percent of Caucasian women.

LASER FOCUS Researchers are targeting why triple negative breast cancer is so aggressive and ways to predict the risk factors among women.

Taking aim at breast cancer’s triple threat

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“Triple negative” breast cancer gets its name because the cells test negative for three known protein receptors — estrogen, progesterone and HER2.

Right now these receptors are the only treatment targets for today’s breast cancer medicines.

“TNBC is fast-growing, metastasizes quickly and carries the burden of poor survival,” explained Senior Clinical Scientist Jennifer Sims-Mourtada, Ph.D., at the Center for Translational Cancer Research (CTCR). “We want to find out what is driving development of TNBC, so we can more accurately predict the risk of this aggressive cancer among all women in Delaware and to determine how external risk factors among different population groups play a role to try to mitigate those risks.”

Dr. Sims-Mourtada and her team are testing the hypothesis that the body’s response to inflammation contributes to the development and growth of breast cancer, and may also determine what type of breast cancer develops.

The researchers are collaborating with Swati Pradham-Bhatt, Ph.D., director of the CTCR’s tissue engineering group, to grow and study TNBC cells in the lab and to use them to test

currently approved anti-inflammatory drugs, some of which may potentially improve treatment outcomes for women with TNBC.

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TNBC is fast-growing, metastasizes quickly ...

We want to find out what is driving its development so we can more accurately predict the risks and mitigate them.

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JEN N I F ER S I MS - MO U R TA DA , P H .D.

Previously, Dr. Sims-Mourtada’s research showed that a growth factor associated with inflammation and wound healing, known as the hedgehog pathway, can promote the growth of highly resistant cells after treatment with radiation and chemotherapy. Her

team is currently investigating how chemotherapy and radiation may activate the transformation of tumor cells into stem-like cancer cells that show increased resistance and the potential to spread or metastasize.

Because TNBC does not always have the suspicious mammographic features of breast cancer, it is likely to be missed on routine mammographic screening.

Better diagnostic tools are needed.

To that end, Dr. Sims-Mourtada’s lab is also working to develop a blood test that one day could be used as a tool for the initial diagnosis of TNBC, as well as to monitor disease progression over time to guide further treatment.

Dr. Sims-Mourtada’s research on TNBC is an important component of a broad research initiative, launched by the Graham Cancer Center and Christiana Care’s Breast Health program, to improve the lives of breast cancer patients and eliminate disparities in breast cancer outcomes in Delaware and communities throughout the nation. ¤

Jennifer Sims-Mourtada, PhD., (second from left) and her team at the Center for Translational Cancer Research are driving research into an aggressive form of breast cancer.

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Progress Toward Personalized Genetic Medicine

Technology teamwork

The Helen F. Graham Cancer Center & Research Institute and The Wistar Institute in Philadelphia are working together to advance early detection and treatment of cancer. This unique community cancer center /academic science collaboration started just five years ago.

Their collaboration has led to a recent announcement by OncoCyte, a developer of new, non-invasive products for cancer detection, about its global licensing agreement to acquire exclusive commercial rights to a revolutionary noninvasive blood test to detect lung cancer at its earliest stages.

Wistar scientists could not have developed the test without access to essential patient samples provided by the Graham Cancer Center and the collaborative efforts of the Thoracic multidisciplinary team.

Led by Louise C. Showe, Ph.D., professor in the Molecular and Cellular Oncogenesis Program at Wistar, researchers identified a panel of biomarkers circulating in the blood that could detect lung cancer in high-risk patients. Dr. Showe’s research into a potential lung cancer diagnostic began in 2004, with funding support provided by The Pennsylvania Department of Health Tobacco Settlement CURE funds.

Subsequent funding helped bring the technology closer to commercialization and a licensing agreement with OncoCyte early this year.

Dario C. Altieri, M.D., president and CEO of The Wistar Institute and director of the Wistar Institute Cancer Center (right) and Nicholas J. Petrelli, M.D., Bank of America endowed medical director of the Helen F. Graham Cancer Center & Research Institute.

with The Wistar Institute, one of the first National Cancer Institute (NCI)-designated cancer research centers and the first solely devoted to researching the biology of cancer.

The Graham Cancer Center was one of the original NCIselected Community Cancer Centers and is presently a National Cancer Institute Community Oncology Research Program (NCORP).

Speeding R&D on first commercial blood test to detect lung cancer at its earliest stages

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WORKING WITH WISTAR Gregory Masters, M.D., principal investigator at the Helen F. Graham Cancer Center & Research Institute reviews genetic samples from the Tissue Procurement Center. This vital data helps translational cancer researchers develop a test that can confirm an early and accurate diagnosis of lung cancer.

Louise C. Showe, Ph.D., (left) of The Wistar Institute

“It is truly remarkable when a community cancer center like the Graham Cancer Center and a leading biomedical research institute like Wistar can combine each’s strengths and come together to advance important scientific discoveries. The Graham Cancer Center has been an ideal partner.” said Dario C. Altieri, M.D., Wistar president and CEO, and director of The Wistar Institute Cancer Center.

The Graham Cancer Center’s Tissue Procurement Center has banked tissue specimens for Wistar researchers to use, which will ultimately aid the pace of discovery in cancer medicine from their lab to clinical trials with the goal of benefiting patients in the community. The collaboration was the first of its kind and brings together the Graham Cancer Center

“The Partnership with Wistar and the Graham Cancer Center allows a basic science research discovery to move rapidly through the development stages to reach its clinical potential. This is possible due to our access to a large patient population and the commitment our clinicians show to translational cancer research,” said Gregory Masters, M.D., one of the investigators for this project at the Graham Cancer Center and principal investigator of the NCORP grant.

With this new assay in its final development stages, the hope is that this test can confirm a patient’s diagnosis and address the high false positive rate obtained via low-dose computed tomography, currently the gold standard for early lung cancer diagnosis. If successful scientific results are achieved, OncoCyte will work with Wistar to fully validate the test in 2016 and set up its commercial launch.

The need for an effective early diagnostic tool is especially dire in lung cancer, where patients have an 80 percent chance of five-year survival after diagnosis in the earliest stages, but only a 1 percent chance if found in stage IV, when it is commonly diagnosed and difficult to treat. ¤ May 2016

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Revolutionary new treatment CO N T I N U E D

The Helen F. Graham Cancer Center & Research Institute hailed as “thriving” model of academic-community cancer centers pushing science toward better treatment options A recent article in MedPage Today featured the Helen F. Graham Cancer Center & Research Institute among a small group of community cancer centers successfully developing models of care that combine the best of academic research with community cancer medicine.

The article, a follow-up to one last summer, highlighted the Graham Cancer Center’s continuing efforts to expand both physician recruitment and academic collaborations that speed discoveries from bench to bedside.

The FDA recently approved Optune in combination with temozolamide to treat newly diagnosed GBM, following publication of the EF-14 multinational clinical trial. Overall survival improved significantly among newly diagnosed GBM

Cancer researchers win top award at national conference progenitor cells from human salivary tissue and demonstrated their directed differentiation into cell types capable of secreting salivary proteins. The project is funded in part by an R01 grant from the National Institutes of Health, on which Dr. Witt is the principal investigator, and Dr. Pradhan-Bhatt, co-investigator, in collaboration with the University of Delaware’s Xinqiao Jia, Ph.D., and Cindy Farach-Carson, Ph.D., at Rice University. ¤

Nicholas J. Petrelli, M.D., Bank of America endowed medical director of the Graham Cancer Center, told MedPage Today that the Graham Cancer Center and The Wistar Institute of Philadelphia are pursuing the next phase of their historic five-year partnership to apply to become a joint National Cancer Institute-designated cancer center, the first of its kind.

By combining resources and expertise, the partners have accelerated translational research in several areas, including the discovery of a gene as a circulating biomarker for non-small cell lung cancer by a Wistar scientist, which is being used to test patients in an IRB-approved protocol at the Graham Cancer Center, as well as in a statewide Delaware lung-cancer screening program. ¤

Padma Pradeepa Srinivasan, Ph.D.

Nicholas J. Petrelli, M.D.

The Helen F. Graham Cancer Center & Research Institute’s tissue engineering work recently won first place at the American Association for Dental Research Hatton Competition, held March 16, 2016, in Los Angeles.

Revolutionary new treatment extends survival with brain cancer Radiation oncologists at the Helen F. Graham Cancer Center & Research Institute are excited to offer a new treatment option for patients with glioblastoma (GBM), the most common and deadliest form of brain cancer.

The tissue engineering team, led by Swati Pradhan-Bhatt, Ph.D., and Robert Witt, M.D., FACS, is nationally recognized for their work with developing bioengineered salivary glands to help relieve some debilitating side effects associated with radiation therapy.

Survival rates have markedly improved for those treated with Optune, a new, non-invasive technology that uses high frequency electrical fields, called Tumor Treating Fields (TTFields), to cripple and destroy cancer cells.

Optune is portable and designed to be worn day and night.

Treatment is delivered through four transducer arrays placed on the shaved scalp and then tuned to focus coverage on the tumor.

“The results are really remarkable, considering that we have seen no significant advances in GBM survival rates over the last 10 to 15 years,” said Radiation Oncologist Sunjay Shah, M.D. “We haven’t changed our primary treatment paradigm for glioblastoma, but by adding this remarkably well-tolerated therapy, we expect that outcomes will improve for many patients.”

patients in that trial, with a 50 percent increase in the number of patients alive two-years after starting treatment with TTFields in combination with temozolomide as compared to treatment with temozolomide alone. ¤

The winning presentation, entitled “Salivary Gland Regeneration Using Differentiated Populations from Human Stem/Progenitor Cells,” was given by post-doctoral researcher Padma Pradeepa Srinivasan, Ph.D., who will represent the team at the International Association for Dental Research Hatton competition held in Seoul, Korea this June.

In their lab at the Center for Translational Cancer Research, the tissue engineering team has successfully isolated stem/

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Progenitor cells from human salivary tissue

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Tamisha Boone

Sunjay Shah, M.D.

An estimated 12,500 people in the United States are diagnosed with GBM each year. This cancer is hard to treat because of where it appears in the brain, particularly in the areas that control thinking, language and movement.

Until now, the median survival time for newly diagnosed patients has been only 12 to 15 months following standard treatment with surgical resection, radiation therapy, and chemotherapy with a drug called temozolomide.

Pat i ent /Physi ci an Coordi nat or

“My job is to ensure each patient appointment runs smoothly, from gathering medical records to coordinating follow-up care. I also prepare patients for their exam or procedure, charting height, weight and blood pressure, for example. As a cancer survivor myself, I share their fight, and I know what I do matters. I take pride in helping patients and their families feel welcome and confident that we are all going to do our best for them.” ¤

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The Multidisciplinary Cancer Centers at the Helen F. Graham Cancer Center & Research Institute offer comprehensive care and treatment.

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Learn how we are transforming cancer care and treatment at www.christianacare.org/cancer Christiana Care is a private, not-for-profit regional health care system that relies in part on the generosity of individuals, foundations and corporations to fulfill its mission. To learn more about our mission, please visit christianacare.org/donors.

Cancer Update is produced by Christiana Care Health System. Š Christiana Care Health System, 2016. All rights reserved.

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