Cancer Update November 2017

N OV E M B E R 2 0 1 6 Is sue No. 34 IN T HIS IS S UE 6 SURGICAL ROBOTS: Performing and pioneering roboticassisted techniques 8 MEDICAL GENETICS: Personalized medicine is a family affair 10 GENE EDITING: Unlocking the genetic mechanizims that drive cancer

The Genitourinary and Prostate Cancer Multidisciplinary Clinic at the Helen F. Graham Cancer Center & Research Institute

Advanced therapy for genitourinary cancers STORY ON PAGE 2

Team members from left: Dhaval Shah, M.D., Christine Omwenga, RN, MSN, MBA, OCN, Adam Raben, M.D., Viroon Donavanik, M.D., Dan Hamm, RN, Chris Mitchell, M.D., Nicole Duffy, Ph.D.

G

E

N

I

T

O

U

R

I

N

A

R

Y

&

P

R

O

S

T

A

T

E

C

A

N

C

E

R

ADVANCED THERAPY

W

hen back pain sent him to his doctor’s office last summer, Cameron Martin figured it was simply the consequence of too many warrior weekends in the garden.

He couldn’t have been more wrong.

S

Medical Oncologist Dhaval Shah, M.D., suggested Martin was a good candidate for an open clinical trial comparing the effects of standard hormone therapy alone to what happens when adding a new investigational drug, TAK-700.

“We had a very short window of time for enrollment, and my research nurse coordinator Louise Brady, RN, BSN, OCN, did a wonderful job, setting up all the necessary testing appointments and filing all the paperwork,” Martin said.

“The level of teamwork really impressed me, and now I know what to expect going forward,” he added. “Like others, I have read all about how the Graham Cancer Center is a top-notch organization, but now I’ve experienced it first-hand, having met the people who work there and realizing what a good job they do.”

Team work across medical specialties Sometimes the best treatment for genitourinary cancers requires a multidisciplinary approach that combines surgery, medical oncology and radiation oncology. The Graham Cancer Center model of multidisciplinary cancer care has become the standard for leading institutions around the country and abroad.

Medical Oncologist Dhaval Shah, M.D., examines Cameron Martin as Research Nurse Coordinator Louise Brady, RN, BSN, OCN, looks on.

After some physical therapy and follow-up testing, his doctor confirmed the diagnosis. “He said it was pretty serious,” Martin recalls. “I had cancer in my lower back, but it was coming from someplace else.”

It turned out that at age 74, Martin had metastatic prostate cancer. “I thought I was relatively healthy, but I hadn’t really kept up with the kind of screening tests that might have found this sooner,” he said.

2

After prescribing hormone therapy and a bone-strengthening agent, his urologist, Michael Lobis, M.D., referred Cameron to the Genitourinary and Prostate Cancer Multidisciplinary Clinic (MDC) at the Helen F. Graham Cancer Center & Research Institute.

“This approach turned out to be terrific,” Martin said. “I had a whole group of medical professionals with a lot of experience and knowledge, who were not only taking care of patients but doing research as well. They were

HELEN F. GRAHAM CANCER CENTER & RESEARCH INSTITUTE

Depending on the patient’s individual needs, experts in other fields may join

“

We offer a full range of advanced therapies for genitourinary cancers, many of which are available at only a few centers in the country.

„

D H A B A L S H A H , M.D.

the team. Each team sits down with the patient and family members to discuss every option and provide the decision-making tools the patient needs to choose what he or she feels is the right course of treatment.

In addition, the Graham Cancer Center offers a host of specialized services, including survivorship, pain and symptom management, genetic counseling, wellness and well-being programs, pastoral care, smoking cessation and a follow-up clinic for young adults who have survived childhood cancer.

“At the Graham Center, we offer a full range of advanced therapies for genitourinary cancers, many of which are available at only a few cancer centers in the country,” Dr. Shah said. “This includes all the approved targeted, anti-hormone

therapies (bicalutamide, abiraterone & enzalutamide) for prostate cancer, as well as vaccine therapy (Provenge) and traditional chemotherapy (taxotere & cabazitaxel).

Immunotherapy (PD-1 Inhibitor) is now approved for kidney and bladder cancer, as are multiple approved targeted drugs and chemotherapy combinations (including anti-tumor agents such as Mitomycin-C for bladder cancer). In addition, our interventional radiologists and urologists may suggest focal therapy with freezing, heat or electricity to target small, localized tumors in the kidney or prostate, for example.

Our surgical expertise encompasses both nerve- and organ-sparing procedures and advanced reconstructive techniques, as well as minimally invasive, laparoscopic and robotic surgery under the direction of Christopher Mitchell, M.D., co-director of Robotic Surgery at Christiana Care (see article page 5). Less invasive surgical techniques shorten hospital stays and improve recovery.

“Often the most effective way to treat prostate cancer is prostatectomy — surgical removal of the prostate,” said Dr. Mitchell. “Robotic surgery enhances the surgeon’s ability to access the prostate, deep within the body, without causing harm to surrounding, delicate, high-stakes anatomy such as the urethra, which controls urination, C ONTINU ED

all willing to help me as much as anyone possibly could.”

Martin’s experience with the MDC changed his mind about going elsewhere for treatment or a second opinion. “The treatment you receive at the Graham Cancer Center is the standard for the type of cancer you have, and it is sanctioned by the National Cancer Institute. I realized I didn’t need to go out of state. I am getting the best treatment right here.”

“I had a whole group of medical professionals with a lot of experience and knowledge, who were not only taking care of patients but doing research as well.

They were all willing to help me as much as anyone possibly could.” Cameron Martin

CO N T I N U E D

November 2016

CA N C E R U P DAT E

3

G

E

N

I

T

O

ADVANCED THERAPY

U

R

I

N

A

R

Y

&

P

R

O

S

T

A

T

E

C

A

N

C

E

R

S

| CONTINUED

“For patients presenting with testicular seminomas, treatment guidelines have changed over the last several years to include active surveillance as a favorable alternative, which is now widely recommended.” Dr. Raben added. “For other patients, a short course of chemotherapy as an alternative to radiotherapy may be appropriate.”

Access to the latest therapies

The Radiation Oncology Department’s newest generation linear accelerator, the Elekta Versa HD, uses ultra-sophisticated technology capable of delivering both conventional and high-dose-rate radiation therapy, faster and more accurately for a wide range of cancers.

neurovascular bundles associated with erection and the rectum. At Christiana Care, 95 percent of prostatectomies are now performed using these advanced robotic surgical techniques.”

Comprehensive alternative strategies to surgery for patients with favorable, intermediate and localized high-risk prostate cancer have been developed through the MDCs and have demonstrated high success rates. Brachytherapy (radioactive seed implants), for example, produces 10-year cure rates that are equivalent to surgery for favorable and intermediate risk disease.

“

For aggressive cancers of the prostate we see excellent results with combined treatment approaches.

„

A DA M R A B E N , M .D.

4

“For aggressive cancers of the prostate we see excellent results with combined treatment approaches, including hormone therapy, brachytherapy and external radiotherapy,” said Adam Raben, M.D., chair of Radiation Oncology at the Graham Cancer Center.

“We are also one of the few centers in the region to offer CyberKnife, a robotic radiation technology, as an alternative to surgery, which affords millimeter accuracy and shortens the overall course of external radiation, significantly.”

According to Dr. Raben, advanced IMRT intensity-modulated radiation therapy is one of the backbone alternatives to surgery for prostate cancer.

“With IMRT we have the added benefit of daily image guidance to detect even subtle tumor changes for precision and accuracy in planning and set-up prior to treatment.”

“Radiotherapy remains the cornerstone of adjuvant (added to primary) treatment when indicated,” Dr. Raben added. For patients with bladder cancer, radiotherapy in combination with chemotherapy or immunotherapy is available as an alternative to surgery in selected clinical settings.

HELEN F. GRAHAM CANCER CENTER & RESEARCH INSTITUTE

As a member of the NCI’s Community Oncology Research Program, the Graham Cancer Center ranks among the nation’s top recruiters of patients to clinical trials, at five times the national average. Ongoing clinical trials such as the one Cameron is enrolled in, offer patients with GU tract cancers the very latest, and often most promising, therapies.

There is an open trial looking at post-operative radiation treatment for bladder cancer, and enrollment begins soon to compare standard chemotherapy to the addition of a PD-1 inhibitor (immunotherapy) for the initial treatment of advanced (stage IV) bladder cancer.

Other clinical trials are looking to answer questions about the duration and scope of different treatments, such as treating pelvic lymph nodes during radiation, or the optimal course of treatment for hormone therapy combined with radiotherapy to improve outcomes and reduce treatment-related complications. New trials are being added to the list regularly.

S U R G E R Y

|

The Advantages of Robots

Robots make expert surgeons even better at treating GU tract conditions At Christiana Care our surgeons are performing and even pioneering, robotassisted surgery for a variety of benign and cancerous genitourinary tract conditions.

Robotic surgery offers many important advantages over traditional, open surgical techniques. “The use of a robotic platform allows the surgeon to perform very complex tasks through very small incisions,” explained Christopher Mitchell, M.D., co-director of Robotic Surgery at the Helen F. Graham Cancer Center & Research Institute. “This ultimately leads to better healing and better outcomes for our patients.”

Dr. Mitchell and his team specialize in minimally invasive, laparoscopic and robotic surgical techniques to treat diseases of the genitourinary tract, including partial nephretomy for kidney tumors, prostatectomy for prostate cancer and complex ureteral reconstruction. Procedures include ureteral reimplantaion to fix the tubes that connect the bladder to the kidneys and a technique called a Boari flap.

Dr. Michell’s expertise also positions Christiana Care among only a handful of centers in the U.S. to offer holmium laser enucleation of the prostate (HoLEP).

This new procedure is shown to be highly effective in treating enlarged prostate or BPH (benign prostate hyperplasia), a non-cancerous condition that affects most men as they age.

“What once required open surgery to remove a very large prostate, for example, can now be done with no incisions whatsoever,” Dr. Mitchell said. Because HoLEP is laser based, there is less bleeding compared to standard transurethral resection (TURP), the catheter stays in a shorter amount of time, and patients can recover and heal faster.

For prostate cancer patients who are good surgical candidates, prostatectomy — surgically removing the prostate — is the most effective treatment. When it comes to prostate surgery, millimeters count.

Robotic surgery increases a surgeon’s ability to access the pelvis and see what is going on inside, without endangering delicate neurovascular anatomy.

“

It’s not just about the robot but the team behind it...that ultimately enhances the patient experience and produces the best outcomes.

„

“The robot can do everything a surgeon’s hand can do and with even greater precision,” said Dr. Mitchell. “Three-D visualization and magnification allows the surgeon to see fine details with more clarity than the naked eye alone.”

Smaller incisions and more precise movements mean less trauma, less pain for patients and less bleeding, reducing the need for blood transfusions as well as the risk of infection. Patients spend less time in the hospital and can return to normal activities much sooner.

Currently Christiana Care has three DaVinci robots, two at Christiana Hospital and one at Wilmington Hospital. The robots are used in about 100 surgeries each month.

“That volume is important because when we do these complex surgeries routinely, the outcomes are better,” Dr. Mitchell said. “It is not just the robot but the team behind it, our surgeons, anesthesiologists, and surgical technicians that ultimately enhances the patient experience and produces the best outcomes.” ¤

C H RI S T O P H ER MI T C H EL L , M.D.

Evidence suggests that patients do better when enrolled in a clinical trial and when treated at centers with high clinical trial accruals. Martin would agree. “I vowed I was going to fight this thing, and with the help of my medical team, I feel we are winning the battle.” ¤

November 2016

CA N C E R U P DAT E

5

G E N E T I C S

|

The Forefront of Personalized Medicine

Medical Genetics

a global force for better medicine

Medical Genetics is making its way to the forefront of health care with personalized medicine.

Genetics can help individuals and families pinpoint hereditary factors that increase our chance of developing disease that may run in our families.

We know, for example, that our risk for some diseases, including hereditary heart disease and some types of cancer, can come from changes in genes we inherit from blood relatives. Identifying the hereditary causes of human diseases through medical genetics can provide the tools doctors need to begin to customize disease prevention and treatment.

The Genetics Risk Assessment Program at the Helen F. Graham Cancer Center & Research Institute offers consultation for hereditary cancer syndromes, adultonset hereditary conditions, transition for childhoodonset hereditary syndromes, and, in conjunction with the Center for Heart & Vascular Health, provides hereditary cardiovascular disease counseling. The genetics department also works in conjunction with the Department of Family Medicine to provide services to our Down Syndrome community. The Maternal Fetal Medicine department offers prenatal genetic services on campus, and Reproductive Associates of Delaware offers reproductive genetic counseling.

“As the field of genetics continues to evolve, genetic counseling and risk assessment are transitioning to an essential service across specialties in our health care system,” said Director of Genetic Counseling Zohra Ali-Khan Catts, MS, LCGC. “Our licensed counselors are trained to provide services across the medical continuum, and we are looking at how best to align our programming with a more global approach.”

IT’S A FAMILY AFFAIR Nearly 7,000 families, representing more than 260,000 people from the area whose family histories, in some cases, extend back generations are recorded in into the High-Risk Familial Cancer Registry.

The Genetic Risk Assessment Program identifies and documents disease risk factors that run in families. One of only three statewide programs in the U.S., the High-Risk Familial Cancer Registry currently houses nearly 7,000 families, representing more than 260,000 individuals from Delaware and surrounding communities. In some cases, these family histories extend backward for generations.

The team is also building similar registries for cardiovascular and adult onset diseases.

Having a family member with a disease can place a person at higher risk for developing that disease compared to someone without a similar history. A personal and family medical history, combined with genetic testing, have proven to be valuable tools in targeting individual health problems, tailoring screening and management, and preventing disease.

Genetic testing can confirm or rule out a suspected genetic condition and help determine the chance of developing or passing on a genetic disorder.

Successful examples include testing for hereditary breast and ovarian cancer syndrome (BRCA1 and BRCA2 genes);

6

HELEN F. GRAHAM CANCER CENTER & RESEARCH INSTITUTE

testing for hereditary colon cancer syndromes; and testing for cardiovascular diseases, such as cardiomyopathy and arrhythmia disorders as well as familial hypercholesterolemia (high cholesterol), which can be passed down from one generation to the next.

Genetic testing can also help identify and target rare genetic disorders that may impact us throughout our life, starting with prenatal and newborn screening and continuing through adulthood. Genetic testing can identify individuals at risk for neurological disorders, cancer, cardiovascular disease and connective tissue disorders.

Genetics is also changing how we treat human diseases. For example, advances in pharmacogenetics have led to optimizing medication selection and dosage based on a person’s genetic make-up, opening up a whole new era of personalized medicine.

“

We see medical genetics as a key component in a comprehensive approach to better care for individuals and families in our state and in our region.

„

Z O H R A A L I - K H A N C AT T S , MS , L C GC

Because what we know about genetics is rapidly changing, Ali-Khan Catts advises individuals and families who have had genetic testing in the past and who have a family history of heredity diseases to keep checking with their genetic counselors for updates about testing and new findings. As the technology for genetic testing improves and becomes more cost effective, more genes are discovered, creating new testing options that were not available in the past.

“In the coming years, genetics will be an important driver for how we treat disease and promote health,” said Ali-Khan Catts. “Our genetic counselors and risk assessment team work collaboratively in multidisciplinary settings throughout Christiana Care. We see medical genetics as a key component in a comprehensive approach to better care for individuals and families in our state and in our region.” ¤ November 2016

CA N C E R U P DAT E

7

R E S E A R C H

|

Discovery improves CRISPR/Cas9 gene editing tool

A Game Changer in Cancer Genetics

CRISPR CUTS Gene-editing pioneer Eric Kmiec, Ph.D., leads a team developing techniques for precision that will have vast applications in cancer and genetic research.

Genetic researchers at Christiana Care’s Gene Editing Institute at the Helen F. Graham Cancer Center & Research Institute are developing the next generation of precision genetic tools to manipulate and control genetic material.

Using these tools to unlock the genetic mechanisms that drive cancer, scientists are working toward new therapies and pharmaceuticals to revolutionize cancer treatment.

Kelly Banas, Gene Editing Institute research assistant from the University of Delaware.

Breakthrough studies under the direction of gene-editing pioneer Eric Kmiec, Ph.D., have demonstrated that short pieces of synthetic single-stranded DNA, known as oligonucleotides, when used in gene editing with what is called the CRISPR/Cas9 technique, can promote the repair of genetic mutations, help achieve a cleaner “cut” of the gene, and reduce the degree of genetic fraying, or heterogeneity, that occurs during gene editing.

Published in the Sept. 9 issue of the journal Scientific Reports, part of the Nature Publishing Group, the research shows that oligonucleotides can act to hold together the ends of the cut DNA and reduce heterogeneity. The article, titled “Analyses of point mutation repair and allelic heterogeneity generated by CRISPR/Cas9 and single stranded DNA oligonucleotides,” also maps in new detail, through highlevel bioinformatics, what takes place in each part of the gene when a CRISPR cut is made. The technique developed

by Dr. Kmiec to improve the CRISPR/Cas9 gene editing

process is the subject of a provisional patent filed by Christiana Care.

“The applications for this in genetic and cancer research are vast,” said Dr. Kmiec, lead author of the study and director of the Gene Editing Institute at the Center for Translational Cancer Research located at the Graham Cancer Center. “If you want to repair a genetic mutation, you can’t allow the DNA to be ripped apart when CRISPR makes a cut. You need it to remain intact to execute the repair, and that’s what the oligonucleotide enables us to do.”

Dr. Kmiec described the effect of the oligonucleotide as similar to applying a Band-Aid to the edges of a cut ribbon.

“CRISPR can leave frayed ends in the DNA,” he explained.

“It’s as though you’ve tried to tear a ribbon in two. But for gene therapy you want a clean cut at a precise spot with minimal fraying, so that the ends can re-close. That’s what the oligonucleotide does. It also helps to maintain the cut, like using a Band-Aid to hold the ends together. Without the oligonucleotide, the ends fray and we lose the gene.”

Dr. Kmiec has been studying the gene editing mechanism for many years in the hope of fixing the genetic mutations that cause disease. While researching sickle-cell anemia, he noticed that whenever he and his researchers used the singlestranded DNA molecule, the oligonucleotide, the result was C ONTINU ED

RESEARCH

at Christiana Care’s Gene Editing Institute fine tunes gene editing and mutation repair

Patent pending for breakthrough gene editing tool a first for Christiana Care

Director Eric Kmiec, Ph.D., and his team at Christiana Care’s Gene Editing Institute have filed for a provisional patent on their discovery of a new gene-editing tool using CRISPR/Cas9 technologies. Ultimately an approved scientific patent on what constitutes a new and improved method cleancutting DNA would be a first for Christiana Care.

Recently, the team published results of its breakthrough discovery that combines CRISPRs and single-stranded DNA oligodeoxynucleotides — short strands of synthetic DNA — to heighten precision and reliability in editing the human genome. This improved method promises to propel genetic research toward new treatments for cancer and many other diseases.

C ONTINU ED

8

HELEN F. GRAHAM CANCER CENTER & RESEARCH INSTITUTE

November 2016

CA N C E R U P DAT E

9

Breakthrough research at Christiana Care’s Gene Editing Institute |

cleaner, and the gene came out healthier and nearly intact. That led them to the discovery that the oligonucleotide was not only helping to repair the mutation but also was preventing the destruction of the gene from fraying or tearing.

“

We are uniquely poised to... accelerate the path of prevention, diagnosis, treatment, and — ultimately — to a cure of cancer.

„

N I C H O L A S J. P E T R E LLI , M .D.

The next step for the research team will be to move from laboratory model cells to human progenitor cells. A federal biosafety and ethics panel recently approved the first use of the CRISPR-Cas9 technique in human patients, and Dr. Kmiec looks forward to that stage in his own research.

“That’s exactly where all of us in this field are headed,” said Dr. Kmiec, “and Christiana Care will be right there on the playing field.”

Along with Dr. Kmiec, authors of the study include, from the Gene Editing Institute, Pawel Bialk and Brett Sansbury, a University of Delaware graduate student; Natalia Rivera-Torres, of the University of Delaware; and Kevin Bloh, of the Gene Editing Institute and the Nemours Center for Childhood Cancer Research.

Christiana Care’s Gene Editing Institute, a world leader in personalized genetic medicine, recently entered a partnership with Philadelphia’s Wistar Institute to accelerate cancer research in the human genome. Working through Wistar’s Molecular Screening Facility, Gene Institute scientists will share innovative geneediting technologies with researchers at Wistar, as well as with external users.

The two organizations have already begun scientific collaborations involving research on melanoma and lung cancer.

“With the addition of the Gene Editing Institute to The Wistar-Graham Cancer Center partnership, we are uniquely poised to advance the goals of Vice President Biden’s National Cancer Moonshot Initiative to accelerate the path to prevention, diagnosis, treatment, and — ultimately — to a cure of cancer,” said Nicholas J. Petrelli, M.D., Bank of America endowed medical director of the Helen F. Graham Cancer Center & Research Institute. ¤

10

HELEN F. GRAHAM CANCER CENTER & RESEARCH INSTITUTE

I N

C ON T I NUED

Patent pending |

C ON T I NU ED

According to Dr. Kmiec, continuing research has led to even greater precision and a new name for the technology they now call ExACT, short for Excision and Correction Therapy. “We are submitting a new manuscript on our latest work that defines parameters to make CRISPR work even more efficient, leaving fewer scars on the DNA,” Dr. Kmiec explained.

“This type of innovation supported

by Christiana Care allows us to stay on the cutting edge of translational cancer research, where results from the laboratory can be applied in new treatments for patients right here in Delaware,” said Christiana Care Senior Counsel Richard Dashefsky.

“The reality is that the Graham Cancer Center has evolved into much more than a community cancer center, and one of the first to be recognized as a Hybrid Academic Community Cancer Center by leading experts and publications.”

“The development of a more precise gene-editing technique is key as we progress toward clinical application in lung cancer and melanoma,” said Dr. Kmiec. “These studies hold promise for using gene editing in combination with well-established chemo or radiation treatment regimens.”

“The melanoma work will be in combination with our outstanding partners at Wistar, while the lung cancer protocol will be developed by our terrific team here at Christiana Care,” he added. “The single most exciting thing to me is that both of these teams are working seamlessly and are completely dedicated to developing a safe and effective therapy.” ¤

Photo above: Gene Editing Institute team members include Natalia Rivera-Torres, MS, researcher, Hailey Weiner, administrative assistant, Pawel Bialk, MS, researcher and Eric Kmiec, Ph.D., director.

T H E

N E W S

|

Community Cancer Centers Impact Medical Science

Helen F. Graham Cancer Center & Research Institute again earns full, 3-year accreditation from ACS Commission on Cancer The Helen F. Graham Cancer Center & Research Institute received Commission on Cancer commendation ratings (the highest possible) in six areas, including praise for “an especially high rate of clinical trials,” five times the national average; excellence in oncology nursing, “at the forefront of patient navigation,” breaking down barriers to care; and in educating the cancer registrars to the National Cancer Data Base, the largest clinical disease registry in the world.

Established in 1922 by the American College of Surgeons, the Commission on Cancer is a consortium of professional organizations dedicated to improving patient outcomes and quality of life for cancer patients through standard-setting, prevention, research, education and the monitoring of comprehensive, quality care. The cancer program at Christiana Care has received Commission on Cancer accreditation since 1951. ¤

Christiana Care surgeon leads drive to clarify cancer-screening guidelines for women with dense breasts Diana Dickson-Witmer, M.D., FACS, surgeon and medical director of the Christiana Care Breast Center and Breast Program at the Helen F. Graham Cancer Center & Research Institute, is the senior author on an article published in the July 11 Annals of Surgical Oncology, outlining an evidenced-based approach to counseling and screening patients with dense breasts.

Currently 27 states, including Delaware, have mandated that mammography reports include information about a woman’s breast density, and that she talk with her doctor about the benefits of additional screening with MRI, 3-D mammography or ultrasound.

Also, Dr. Dickson-Witmer was elected to serve a minimum three-year term on the Breast Cancer Steering Committee’s Breast Oncology Local Disease Task Force of the Delaware/Christiana Care NCI Community Oncology Research Program (NCORP). Through NCORP, Christiana Care is broadening access for patients living and working in communities across our state to latest cancer clinical trials (cancer control, prevention, screening, treatment, and imaging). ¤

Dr. Dickson-Witmer

Christiana Care gynecologic oncologists aid in discovery of new treatment target for ovarian cancer Gynecologic oncologists at the Helen F. Graham Cancer Center & Research Institute collaborated with research scientists at The Wistar Institute in Philadelphia to discover a promising new treatment target for ovarian cancer.

“This discovery may allow us to overcome one of the greatest obstacles in using immunotherapy to treat ovarian cancer by identifying a marker that is present only on the cancer cells,” said Mark Cadungog, M.D., gynecologic oncologist and director of robotic surgery at Christiana Care, who is a co-author on the study.

Dr. Cadungog along with Gynecologic Oncology Division Director Mark Borowsky, M.D., and Stephanie Jean, M.D., director of Gynecological Oncology Research, collaborated with José R. Conejo-Garcia, M.D., Ph.D., professor and program leader of Wistar’s Tumor Microenvironment and Metastasis Program, providing blood and tissue samples for study.

Drs. Cadungog, Borowsky and Jean

Their findings, published in the journal Clinical Cancer Research, are an important step toward one day using immunotherapy as an adjunct to surgery and chemotherapy to help prevent ovarian cancer recurrence, a major concern for women with advanced stages of disease. ¤ November 2016

CA N C E R U P DAT E

11

I N

T H E

N E W S

|

Community Cancer Centers Impact Medical Science

Christiana Care shares authorship on NEJM study providing better control of chemotherapy-induced nausea and vomiting Chemotherapy patients at the Christiana Care Helen F. Graham Cancer Center & Research Institute helped test a drug called olanzapine (Zyprexa) that proved highly effective in controlling symptoms of nausea and vomiting during treatment for ovarian, breast, lung and head and neck cancers.

Medical Oncology Section Chief David Biggs, M.D., was the top local enroller in the study and a co-author of the report published in the July 2016 issue of the New England Journal of Medicine. ¤

Christiana Care resident to serve on premier radiation oncology society science subcommittee Radiation Oncology resident, Serguei Castaneda, M.D., (PGY-3) will serve on the American Society of Radiation Oncology (ASTRO) Clinical, Translational and Basic Science Advisory Subcommittee for the term 2016-2017. He also serves on the Global Health Subcommittee of ASTRO, the world’s leading radiation society.

Dr. Castaneda, (PGY-3) was the first resident to enter the Helen F. Graham Cancer Center & Research Institute’s fully accredited radiation oncology residency program launched with Drexel College of Medicine and Hahnemann Hospital in 2015. The Graham Cancer Center is the primary clinical

T

E

A

M

W O R

K

|

site for the program, which includes rotations at Hahnemann University Hospital and Drexel University.

According to Residency Program Director Jon Strasser, M.D., very few residents are appointed to ASTRO subcommittees.

“Dr. Castaneda has done a great job as a resident clinically, and has had several excellent research projects already presented at national meetings,” said Dr. Strasser. “His appointment to two ASTRO subcommittees is a testament to Dr. Castaneda’s growing expertise in these areas.” ¤

Specialists in your corner

Surgeon Gregory J. Tiesi, M.D., joins our multidisciplinary team of experts to partner in your care Dr. Biggs and trial participant Teresa Dessin discuss the study.

Gregory J. Tiesi, M.D., has joined the Helen F. Graham Cancer Center & Research Institute and the Bennett/Abdel-Misih Group in Newark, Delaware.

Dr. Tiesi completed his general surgery training at Rutgers-New Jersey Medical School in Newark, N.J., where he participated in a research fellowship devoted treating of advanced peritoneal malignancies with newer treatment modalities such as hyperthermic intraperitoneal chemotherapy (HIPEC). During this time, he was twice awarded the Arnold P. Gold Foundation award for Humanism and was inducted into the Alpha Omega Alpha Honor Medical Society, Beta Chapter.

Christiana Care cancer specialists aid in discovery of marker to identify cells that block our natural defenses against cancer Medical and surgical oncologists at the Helen F. Graham Cancer Center & Research Institute collaborated with research scientists at The Wistar Institute in Philadelphia to discover a marker for myeloid-derived suppressor cells (MDSC), implicated in tumor resistance to various types of cancer treatments.

According to Robert Witt, M.D., FACS, director of the Graham Cancer Center’s Head and Neck Multidisciplinary Clinic, “These cells multiply in patients with cancer and prevent the body from forming an immune response to fight it. Finding genes that helps indentify these cells is key to developing a targeted treatment to improve patient outcomes.”

He subsequently completed a fellowship in complex general surgical oncology at the University of Miami where he treated a wide array of complicated cancers employing advanced techniques including Irreversible Electroporation for advanced pancreatic and liver cancers.

Dr. Nam

Dr. Tiesi is the author of several articles published in peer-reviewed journals on multiple topics including HIPEC and esophageal cancer, book chapters on topics including the treatment of bile duct cancers and abstracts. He has presented on various general surgery and oncology topics on both national and international scientific platforms and has won several awards including the 31st Annual SSAT Residents and Fellows Research Conference Award. ¤

F E A T U R E D

Dr. Witt, an internationally recognized surgeon and researcher in salivary gland and thyroid cancer, joined with head and neck surgeon Neal Hockstein, M.D., thoracic surgeon Brian Nam, M.D., and lung cancer expert Greg Masters, M.D., as co-authors on the Wistar’s study, published in the journal Science Immunology.

Jayne H. Logue, RTR Radi ol ogi c Technol ogi st Drs. Witt and Hockstein

Their partnership included facilitating shipments of throat and neck tumor tissue, given with permission from Christiana Care patients, to the lab of Dmitry Gabrilovich, M.D., Ph.D., senior author on the study and Christopher M. Davis professor and program leader of the Translational Tumor Immunology program at Wistar. ¤ Dr. Masters

12

HELEN F. GRAHAM CANCER CENTER & RESEARCH INSTITUTE

E M P L O Y E E

“My job as a radiologic technologist involves more than conducting imaging studies and X-rays. It allows me to extend a hand for support, lend an ear for empathy and always give a smile for hope and understanding. I feel privileged to be part of the Graham Cancer Center team working with an everchanging technology that helps to improve the lives of those battling cancer.

We are working everyday to find a cure through clinical trials and intense research. As an important link to this mission, I try to be dependable, kind and encouraging, as well as accurate and confident in the work that I do. ¤

November 2016

CA N C E R U P DAT E

13

CHRIS T I AN A C ARE C ANCER PROGR AM 2015 AN ALY T IC* C A SE DIS T RIBU T ION YEAR CASES SEEN AT CHRISTIANA CARE HEALTH SYSTEM

Clinical capsule

PRIMARY SITE

Minimizing repeat visits to the OR for women who choose breast-conserving surgery, improves value and patient well-being

2008

2009

2010

2011

2012

2013

2014

2015

ORAL

68

73

78

87

74

82

96

110

Tongue

26

25

26

29

25

27

26

33

Mouth

29

41

45

47

34

48

62

Pharynx

13

7

7

11

15

7

8

DIGESTIVE

460

498

442

433

473

460

Esophagus

29

36

29

20

39

Stomach

35

34

25

32

30

Small Intestine

The data showed that in 94 percent of cases, surgeons followed national guidelines for when re-excision is indicated. However, in many cases, when the pathologist examined the tumor under a microscope, cancer cells remained at the edges of the tumor, what is called a positive margin. This high positive margin rate led to a higher than national average re-excision rate.

The data collection period for the study straddled the publication of the national guidelines for re-excision (by ASTRO/SSO), so the expectation was to see some early adopters of the guidelines and surgeons who were

As part of the quality improvement process, surgeons are counseled regarding their positive margin rates, benchmarked against national data The pathologist uses special ink and the rates of other Christiana Care to delineate the tumor under the surgeons. Real-time tracking of positive microscope. The guidelines say that margin rates is ongoing for the three as long as there is no ink touching busiest breast surgeons. We have the tumor, a return to the operating also promulgated the “shave margin” room is not necessary. This new “no technique, which involves removing ink on tumor” rule could cut in half a circumference of tissue around the the number of times a woman has to entire margin of the tumor cavity, endure repeat surgeries to ensure a All units ICUs a procedure Anees B. SumOfCAUTI_Device_Days good outcome.

Calendar_Year_Month SumOfCAUTI_Infec;on_Count SumOfCAUTI_Device_Days CAUTI Rate Rolling 6shown monthsby SumOfCAUTI_Infec;on_Count CAUTI Rate Chagpar, Tumor 16 3371 4.75 M.D., MPH., at Yale University, 2 1049 1.91 There was significant variation in to21.67 cut in half the Tumor 48 2215 0.87positive margin rates.4 741 5.40 the positive the2411 The1.66 goal is to 0.07 reduce Christiana Care’s4 4 811 4.93 Not margin rate among surgeonsRe-­‐ studied, and the “ink-on3 2355 1.27 0.05 3 888 3.38 re-excision rate to the national average tumor” positive 2344 0.00percent0.00 4 992 4.03 Residual margin was0the of 25

by July 2017. ¤ Inability to

0

2497

0.00

0.00

5

REASONS FOR RE-EXCISIONS 70

87%

90%

60 50

0%

0%

0 Residual Re-excision recommended suspicious calcifications

by MTB

Inability to evaluate margin

4

20

18

10

52

6

41

3

7

7

4

17

3

62

57

1

11

9

5

28

3

15

12

0

2

2

1

7

0

502

478

526

18

106

105

111

152

34

30

30

31

31

0

5

5

10

9

2

36

42

28

39

0

6

5

11

13

4

8

16

15

13

18

21

8

20

19

1

3

4

3

5

3

Colon

168

179

158

155

138

144

161

147

171

10

38

38

41

37

7

Rectum/Rectosigmoid

76

80

68

72

74

58

76

79

81

5

25

11

27

12

1

Liver/IHBD

35

30

32

36

36

47

46

40

28

0

9

3

4

10

2

Pancreas

69

83

77

69

85

75

90

77

106

0

14

26

7

54

5

Other Digestive

40

40

38

36

53

49

49

56

51

2

6

13

8

12

10

RESPIRATORY

439

465

446

521

469

429

470

481

516

1

143

40

100

219

13

Larynx

21

28

32

29

30

25

29

26

26

1

5

3

7

9

1

Lung

401

421

399

479

426

395

431

438

474

0

131

37

92

205

9

Mesothelioma

9

7

6

8

10

8

5

11

8

0

4

0

1

2

1

Other Respiratory

8

9

9

5

3

9

5

6

8

0

3

0

0

3

2

BONE & CONNECTIVE TISSUE

28

25

28

20

32

20

23

28

28

0

6

3

10

5

4

Bone/Joints

4

7

5

5

5

6

5

1

6

0

1

1

0

1

3

Connective/Soft Tissue

24

18

23

15

27

14

18

27

22

0

5

2

10

4

1

MELANOMA

118

145

160

136

145

108

126

157

123

37

41

22

12

5

6 1

Other Skin Cancer

9

13

6

7

8

13

12

9

5

0

1

1

1

1

BREAST

597

639

703

652

698

747

789

760

721

170

287

193

49

20

2

FEMALE ORGANS

229

198

228

202

257

252

267

245

265

3

156

17

41

35

13

Cervix

48

33

41

41

33

37

30

36

34

0

16

5

10

3

0

Uterus

113

101

110

110

154

152

157

132

163

0

115

6

17

17

8

Ovary

54

37

52

39

53

41

51

48

44

0

11

5

11

15

2

Other Female Organs

14

27

25

12

17

22

29

29

24

3

14

1

3

0

3

MALE ORGANS

407

401

302

285

225

213

218

212

236

0

42

142

22

25

5

Prostate

393

390

290

274

217

204

207

192

222

0

37

139

17

25

4

11

10

8

8

7

9

15

13

0

5

2

5

0

1

0

2

3

0

2

2

5

1

0

0

1

0

0

0

70%

URINARY

188

179

199

215

216

216

218

226

246

70

104

18

19

27

8

60%

Bladder

109

83

104

105

124

115

128

117

131

67

31

14

4

12

3

Kidney/Renal Pelvis

72

89

90

105

89

96

80

101

105

0

71

4

11

15

4

Other Urinary

7

7

5

5

3

5

10

8

10

3

2

0

4

0

1

BRAIN/CNS

113

123

116

112

102

106

90

103

86

0

0

0

0

0

86

ENDOCRINE

95

117

129

133

144

125

142

175

113

0

81

9

8

7

8

20%

Thyroid

69

93

94

108

131

110

120

154

104

0

81

9

7

7

0

10%

Endocrine/Other

26

24

35

25

13

15

22

21

9

0

0

0

1

0

8

LEUKEMIA

68

79

37

53

57

76

46

51

58

0

0

0

0

0

58

0% Not concordant with SSO/ ASTRO

110

1

30%

5%

III

13

40%

7%

II

Other Male Organs

30

10

4.99

I

Testis

50%

20

1003

IV

UNK/ NA

0

80%

40

Tumor present at final inked margin

14

indication for re-excision in over 80 percent of the cases studied.

PERCENT TOTAL

To improve value and the patient experience in cases of breast conserving surgery, the Christiana Care Cancer Committee at the Helen F. Graham Cancer Center & Research Institute studied reasons for re-excision and the re-excision rate by surgeons over a three-year period.

not in compliance. However, the data showed that most Christiana Care surgeons had adopted the “no-ink-ontumor” rule even before the guidelines were published.

NUMBER OF PATIENTS

Approximately 20 to 40 percent of women who have a lumpectomy or breast conserving surgery make repeat trips to the operating room for a second operation based on the pathologist’s report. Re-excisions following breast conserving surgery cost well over $8,500/case, and can cause both physical and psychological pain for the patient.

2015 CASES BY AJCC STAGE GROUPS

2007

Hodgkin Lymphoma

10

20

20

25

15

9

16

14

25

0

5

10

4

5

1

Non-Hodgkin Lymphoma

102

130

126

97

108

86

97

117

117

0

31

25

23

35

3

Myeloma

26

39

28

25

28

34

36

34

28

0

0

0

0

0

28

ALL OTHER/UNDEFINED

58

74

64

79

63

64

54

59

50

0

0

0

0

0

50

3015

3218

3112

3082

3114

3048

3202

3259

3253

303

1023

603

410

588

326

TOTAL HELEN F. GRAHAM CANCER CENTER & RESEARCH INSTITUTE

*Analytic cases involve patients newly diagnosed or who were newly treated by Christiana Care Health System.

Source: Oncology Data Center

PRSRT STD U.S. POSTAGE PAID WILMINGTON DE PERMIT NO. 357

P.O. Box 1668 Wilmington, DE 19899-1668

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

Breast Cancer Bone Sarcoma Genetic Risk Assessment Genitourinary Cancer Head & Neck Cancer/Thyroid Hepatobiliary/Pancreatic Cancers Lymphoma Medical Support Melanoma/Soft Tissue Sarcoma Ostomy Care Rectal/Anal Cancers Skin Screening Thoracic/Esophageal Cancers Young Adult Follow-up

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.

17CANC3