Discovery

UNT I L E V E RY C ANC ER I S C U RED

FALL 2019

FROM THE DIRECTOR

Strategies for Supportive Cancer Care

Karen E. Knudsen, MBA, PhD Executive Vice President Oncology Services Enterprise Director Sidney Kimmel Cancer Center

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t the Sidney Kimmel Cancer Center (SKCC) we are guided daily by our mission — to improve the lives of cancer patients and their families through compassion, innovation, and breakthrough discoveries. This is the focus of every clinician, every scientist, and every staff member in our center, and it distinguishes SKCC as one of only 71 National Cancer Institute (NCI) -designated centers of excellence.

While the challenge to reduce cancer incidence and mortality is immense, this quarter we are buoyed by evidence that our mission, our discoveries, and those of our peer institutions are making a difference. The NCI recently released their Annual Report to the Nation, which reports on long-term trends regarding cancer incidence and mortality rates in the United States. The news was incredibly positive, in that cancer deaths continue to decline amongst men, women, and children as a result of our collective discoveries and conversion of new understanding into clinical practice.

Overall rates of new cancer cases continue to decline among men and remain stable in women, indicating that we are not only treating cancer more effectively, but that efforts for cancer prevention are bearing fruit.

There was also good news regarding cancer disparities, as was reported at the annual ASCO (American Society for Clinical Oncology) meeting, at which SKCC members hold leadership roles. Researchers reported that the racial disparities in timely access to cancer treatment were virtually eliminated in states that adopted Medicaid expansion under the Affordable Care Act (ACA). It was also noted that since the ACA was implemented, women

younger than 65 with ovarian cancer were more likely to be diagnosed at earlier stages, when it is more treatable, and to begin treatment within 30 days. These reports illustrate the need for the cancer community to attend to cancer discovery, cancer care, and also cancer policy.

As it is clear that cancer discovery is improving lives, it is more important than ever for SKCC to attend to the specialized needs of cancer survivors.

As we sharpen our mission, SKCC is now more focused than ever on treating the whole person and not just the cancer. To provide personalized, comprehensive care to our patients, we must also consider their psychological, financial, and social needs, as well as long-term survivorship needs for patients and their families.

This issue of Discovery highlights successes of the Sidney Kimmel Cancer Center – Jefferson Health in providing innovative strategies for supportive cancer care — beginning at diagnosis, in addition to breakthroughs from our scientists and clinicians.

We are proud to provide exceptional cancer care to every patient, and to help lead the way for discoveries that reduce cancer incidence and mortality in Greater Philadelphia and beyond. 

STAY CONNECTED TO THE SIDNEY KIMMEL CANCER CENTER BY VISITING OUR WEBSITE AND FOLLOWING US ON SOCIAL MEDIA!

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CONT ENT S FEATURE ARTICLE

14 SURVIVORSHIP Supportive Care for Cancer Survivors Begins at Diagnosis

4 BREAKTHROUGHS Lymphoma 4 Uveal Melanoma 5 Skin Cancer 6 Prostate Cancer 17 Population Health 20 Glioblastoma 21

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CLINICAL TRIALS Colorectal Cancer 7 Head & Neck Cancer 8 Glioblastoma 9 Lymphoma 16

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SKCC NEWS Gastrointestinal Cancer Program Prostate Cancer Program

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NEW DEVELOPMENT HIGHLIGHTS SURVIVOR STORIES Lou Lanza & John Buehler Arleen Weitz

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19 ACCOL ADES 23 WELCOME CENTER 24 ASPLUNDH CANCER PAVILION News from the north

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WASHINGTON TOWNSHIP

News from New Jersey

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PHIL ANTHROPIC SUPPORT 3

B REAKTHROUGH LYMPHOMA

SKCC Team Sticks a DNA Replication Fork into Lymphoma Development

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new study from Sidney Kimmel Cancer Center – Jefferson Health (SKCC) researchers provides important insights into the role of DNA replication fork remodeling in mitigating stress on DNA caused by dysregulation of the Myc oncogene, which occurs in at least 70 percent of human cancers.

tion forks undergo this process. When problems occur during DNA duplication, specialized proteins involved in the “DNA replication stress response” are called to the site to protect against DNA replication fork collapse and DNA damage that can lead to cell death or mutations that can result in cancer.

Senior author Christine M. Eischen, PhD, co-leader of the Molecular Biology & Genetics Program at SKCC and Herbert A. Rosenthal, MD ’56 Professor in Cancer Research, and colleagues studied the role of two closely related proteins, termed Smarcal1 and Zranb3, which stabilize stalled DNA replication forks, a structural feature of chromosomes in actively dividing cells. When a cell divides, it must duplicate its chromosomes so that a full set is passed on to each of the two daughter cells, and DNA replica-

The SKCC investigators discovered that during lymphoma development induced by the Myc oncogene, Smarcal1 and Zranb3 have non-redundant critical roles in resolving DNA replication stress and are unable to functionally compensate for one another. The new study is the first to directly compare the in vivo functions of these two closely related DNA replication stress response proteins. It also demonstrates that Myc-overexpressing cells lacking either protein exhibit significant differences in replication fork stalling, collapse, and DNA damage, thereby leading to changes in cell proliferation and cell death. These effects were linked to altered B-cell lymphoma development.

Strands of DNA from primary mouse B cells isolated from Zranb3- or Smarcal1deficient Eμ-myc transgenic mice pulse-labeled with IdU (red) and CldU (green) detected by immunofluorescence and microscopy. The technique is called DNA fiber labeling.

Selected for the cover of Cancer Research

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“We have identified replication stress induced by Myc as the first endogenous source of DNA replication stress that requires both proteins for resolution,” Eischen explained.

“Our data greatly enhance understanding of the DNA replication stress response and the essential functions two fork remodeling proteins have in protecting cells from the early stages of cancer development.”

These findings also have potential implications for the clinical development of new cancer treatment strategies. With regard to Smarcal1

Christine M. Eischen, PhD Program Co-leader, Molecular Biology & Genetics Herbert A Rosenthal, MD ‘56 Professor in Cancer Research

and Zranb3, Eischen pointed out that “due to their critical roles in mitigating DNA replication stress caused by an oncogene, targeting one or both of these proteins could be considered for some types of cancer.”

The Eischen laboratory is actively following up on this research by investigating the role of these two proteins in hematopoiesis and immune cell deficiencies that contribute to lymphoma susceptibility. It is anticipated that these studies will contribute to the understanding of the cellular events underlying lymphoma development and will eventually lead to more effective treatments for this class of deadly tumors.

The study was published in the journal Cancer Research. 

BREAKTHROUGH UVEAL MELANOMA

Eyes on the Prize: Developing Better Treatments for Uveal Melanoma

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veal melanoma arises in the eye, often spreading to the liver and becoming highly resistant to treatment.

SKCC researchers investigated the efficacy of a class of inhibitor drugs for these patients. The study, from co-corresponding authors Vivian Chua, PhD, and Andrew Aplin, PhD, was published in EMBO Molecular Medicine.

The group examined the activity of inhibitors that target transcription factors known as bromodomain and extraterminal (BET) proteins. In a clinical trial testing PLX51107, a novel BET inhibitor, liver metastases of uveal melanoma patients progressed rapidly following BET inhibitor treatment, raising the question of how the cancer cells are able to become resistant so quickly. In this study, the researchers identified a mechanism involving a growth factor released by non-tumorous cells near the tumor, which reaches the uveal melanoma and allows melanoma cells to evade growth inhibition by BET inhibitors.

The BET inhibitors were found to induce expression of fibroblast growth factor 2 (FGF2) in stromal cells surrounding the tumor, an effect observed in uveal melanoma cell lines and patient samples. Additionally, the FGF receptor (FGFR) that binds to and is activated by FGF2 was also upregulated by the BET inhibitors in the tumor cells. Taken together, these findings reveal that in uveal melanoma cells treated with BET inhibitors, increased expression of FGFR and its stimulatory ligand secreted from nearby cells causes the tumor cells to boost their growth ability enough to

rapidly become resistant to the inhibitor’s growth-suppressing effects.

“Our study highlights the importance of inhibitor-induced upregulation of certain growth factors and their receptors in promoting the growth of uveal melanoma cells and allowing them to overcome the effects of therapeutic inhibitors,” said Aplin, Kalbach-Newtown Professor in Cancer Research and Associate Director of Basic Research.

“The SKCC uveal melanoma group is truly exceptional and has been fast-tracking discoveries to the clinic through working as a multidisciplinary team.”

The study also has major implications for the design of new clinical trials to improve uveal melanoma treatment.

The team found that combining two inhibitors, PLX51107 to target BET proteins and a second drug, AZD4547, to target FGFR, resulted in a more durable growth suppression of uveal melanoma cells transplanted into mice.

idea that we hope to explore further in the lab and develop into future clinical trials,” Aplin explained.

“These results suggest that co-targeting the FGFR signaling pathway along with the BET proteins might offer an effective new approach to treating uveal melanoma patients, an

The study highlights the strong collaborations between basic scientists and medical oncologists at Wills Eye Institute and Thomas Jefferson University.

MRI scans of the patient’s abdomen preand post-PLX51107 treatment. Increase in size and number of hepatic lesions (red arrows) were observed post-treatment.

Andrew Aplin, PhD Kalbach-Newton Professor in Cancer Research Associate Director, Basic Research Sidney Kimmel Cancer Center

“The SKCC uveal melanoma group is truly exceptional and has been fast-tracking discoveries to the clinic through working as a multidisciplinary team. We are enthusiastic about the translational promise of these findings for developing new ways to treat uveal melanoma,” said Karen E. Knudsen, MBA, PhD, EVP of Oncology Services and Enterprise Director of SKCC. 

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B REAKTHROUGH SKIN CANCER

SKCC Researcher Finds Potential Treatment for Butterfly Disease-Related Cancer

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hildren with the severe skin disease recessive dystrophic epidermolysis bullosa (RDEB), also known as butterfly disease, often develop an aggressive and fatal skin cancer by early adulthood. An SKCC investigator along with an international team of scientists have identified a potential drug treatment for the lethal complication. The discovery paves the way for a clinical trial to begin this year.

a number of cancers, many drugs that block the enzyme already exist. In the preclinical study, the researchers tested how well six anti-PLK1 compounds attacked the RDEB patients’ cancer, and a drug called rigosertib stood out.

The researchers isolated healthy and cancerous cells from 10 patients during routine diagnostic and surgical procedures. When treated with rigosertib, the cancer cells died in all 10 cases.

“We hope that the drug will be a cure for the cancer,” said Andrew South, PhD, Associate Professor, Department of Dermatology and Cutaneous Biology and senior author of the study, which was published in Clinical Cancer Research. “If we can reduce the cancer, or even reduce the spread of the cancer, that is going to improve patients’ quality of life and extend their lifespan.”

“Sixty percent efficacy is something one might think about taking to the clinic, but 100 percent of the cells being responsive to the drug is something I’ve never seen before,” South said.

Patients with RDEB do not make enough of a protein that helps hold layers of the skin together, making it incredibly delicate. The smallest touch can cause damage and lead to persistent blisters. In previous research, South found chronic inflammation and scarring from these wounds spur the development of squamous cell carcinoma. Many people develop this type of skin cancer from sun exposure. It is highly curable when caught early. However, for RDEB patients, the five-year survival rate is close to zero.

South and colleagues previously identified an enzyme involved in cell division called polo-like kinase 1 (PLK1) as a potential drug target for squamous cell carcinoma. As PLK1 is implicated in 6

The drug also specifically targets cancer cells but leaves normal cells unharmed, which was key to rigosertib becoming the lead molecule of those tested.

The researchers then found rigosertib very effective at treating the cancer

Andrew South, PhD Associate Professor, Dermatology and Cutaneous Biology

in preclinical mouse models. Systemic delivery of the drug stopped the cancer’s growth and the tumor cells died. “Epidermolysis bullosa patients’ cancers metastasize very rapidly, so a systemic drug should target all the cancer cells in the patient,” South said.

However, he cautioned that laboratory results do not always indicate a drug will work in people. “One goal of the upcoming trial is to figure out whether rigosertib can reduce the tumor burden in RDEB patients with cancer. Any drug that can do that will improve the current standard of care.”

PLK1 is increased in RDEB squamous cell carcinoma. 6 mm frozen sections were processed and incubated with an antibody raised against PLK1 (SigmaAldrich, HPA053229, red) as well as the nuclear stain DAPI (blue). Bar, 400 mm.

The trial will be led by principal investigator Bahar Dasgeb, MD, of Jefferson’s Adult EB clinic, one of the only clinics for this population in the U.S. 

CLINICAL TRIAL COLORECTAL CANCER

Novel Colorectal Cancer Vaccine Shows Positive Results

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new colorectal cancer vaccine showed positive results in the phase I clinical trial to demonstrate that the approach is safe, according to research published in the Journal for ImmunoTherapy of Cancer. The trial was conducted by Adam Snook, PhD, Assistant Professor, Department of Pharmacology & Experimental Therapeutics, and Sidney Kimmel Cancer Center – Jefferson Health (SKCC) colleagues.

The patients treated had no signs of serious adverse events and their blood samples contained markers of immune activation – an early indication that the vaccine could activate immune cells to fight colorectal tumors and metastases.

Colorectal cancer, especially in younger people, is on the rise and is currently the second leading cause of cancer deaths in the U.S. and worldwide. Surgery can cure the disease for many, but prognosis is poor among those who experience recurrence. If it proves effective in larger scale trials, the vaccine could train the patient’s immune system to attack the colorectal cancer that had already spread before the surgery.

In earlier studies, the researchers demonstrated in mice how the design of their vaccine worked. Tumor vaccines have historically been developed against a kind of molecular signpost for cancer. Because they come from normal cells, cancer cells share nearly all of the same molecules, making it difficult for the immune system to differentiate normal cells from cancerous ones. Tumor anti-

gens are molecules that the immune system can recognize as different.

Scott Waldman, MD, PhD, Samuel M.V. Hamilton Professor and co-leader of SKCC’s Gastrointestinal Cancer Program, identified one such molecule called GUCY2C in colorectal cancer.

The vaccine, which was developed

by Snook, Waldman, and others, works by activating the immune system against the GUCY2C molecule. By joining the GUCY2C molecule with PADRE, a molecule that boosts the immune reaction, and loading it into an adenovirus vector, the researchers engineered a vaccine that could specifically target colorectal cancer.

“The goal of the study to begin this fall is to show that version 2.0 of the vaccine is even better and that it may benefit a much bigger group of the overall cancer patient population.”

The trial enrolled 10 patients with stage I or II colorectal cancer. Patients received one dose and returned for blood draws 30, 90, and 180 days after immunization. Patients experienced some discomfort at the injection site, but reported no serious adverse effects.

The blood samples showed activation of “killer T cells,” the immune cell type the researchers expected. These killer T cells are responsible for finding and killing the colon cancer cells responsible for the cancer’s recurrence.

“We are preparing for a phase II study that will begin recruiting patients this fall,” Snook said. “We used lessons learned in the first study

Adam Snook, PhD Assistant Professor Department of Pharmacology & Experimental Therapeutics

to modify the vaccine to hopefully make it even more effective.”

Since starting the trial, the researchers found additional cancers that express GUCY2C, including gastric, esophageal, and pancreatic.

Together with colorectal cancer, these four cancer types account for 20 percent of all cancer-related deaths.

“The goal of the study to begin this fall is to show that version 2.0 of the vaccine is even better and that it may benefit a much bigger group of the overall cancer patient population,” Snook said. 

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CLINICAL TRIAL HEAD & NECK CANCER

Head & Neck Trial First of Its Kind to Combine Immunotherapy with Metformin

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nvestigators at the Sidney Kimmel Cancer Center – Jefferson Health (SKCC) have begun enrolling patients into a pilot phase I clinical trial to determine how well durvalumab (Imfinzi) given with or without metformin works in treating patients with head and neck squamous cell carcinoma (HNSCC).

HNSCC includes cancers of the nasal cavity, sinuses, mouth, lips, throat, and larynx. According to the National Cancer Institute, HNSCC is the sixth most common cancer in the United States, and HPV-related throat cancer is increasing significantly.

Durvalumab is an immune checkpoint inhibitor that is currently FDA approved to treat patients with certain types of non-small cell lung cancer and bladder cancer. Durvalumab works by targeting PD-L1, an immune checkpoint protein that attaches to cancer-fighting T cells and acts like a brake, stopping the T cells from attacking the tumor. Durvalumab blocks PD-L1, allowing the T cells to better identify and attack the cancer. Metformin is a commonly prescribed drug typically used to treat patients with type 2 diabetes. It may also help reduce the metabolic activity of cancer cells and surrounding supportive tissues.

This trial takes advantage of a system of window-of-opportunity trials that have been successful in the head and neck multidisciplinary disease group, explained Joseph M. Curry, MD, principal investigator and Associate Professor of Head and Neck Surgery and Microvascular Surgery in the Department of Oto-

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laryngology/Head & Neck Surgery.

A window-of-opportunity trial is a study that briefly exposes treatment-naïve patients to an investigational therapy before they receive standard treatment in order to observe tumor biology. Tumor biopsies are usually collected before and after the patients receive the novel therapy.

“We use drugs like immunotherapy prior to surgical resection to assess for a biological response,” Curry said.

“We usually get a biopsy and give one or more doses and then compare pretreatment biopsy to the surgical specimen. This trial capitalizes on a prior trial that we performed using metformin alone in a similar format.

We gave metformin prior to surgery and found changes in cancer-associated fibroblasts and immune markers.”

“While immunotherapy may only be effective in about 15 to 20 percent of recurrent and metastatic cases, it may have more chance of effect if used up front for therapy.”

Curry previously published data from several studies suggesting the metabolic effects of metformin may reverse the tumor-promoting effects of cancer-associated fibroblasts and possibly improve immune cell recruitment to the tumor microenvironment.

“We then designed this trial to use an anti-PD-L1 drug, durvalumab, in combination with metformin to see if we could augment the effect of the durvalumab in fighting the tumor,” said Jennifer Johnson, MD, PhD, lead

Joseph M. Curry, MD Associate Professor, Otolaryngology/ Head & Neck Surgery

medical oncologist on the study.

Immunotherapy is currently being used to treat recurrent and metastatic head and neck cancer, but there are data showing immunotherapy might be more effective than drugs like cetuximab, a type of chemotherapy commonly used to treat HNSCC. “Also, while immunotherapy may only be effective in about 15 to 20 percent of recurrent and metastatic cases, it may have more chance of effect if used up front for therapy,” Curry said.

This trial, which Curry developed in collaboration with Johnson, Ubaldo Martinez-Outschoorn, MD, and Ethan Argiris, MD, in the Department of Medical Oncology, is the first of its kind to combine immunotherapy with metformin. 

CLINICAL TRIAL GLIOBLASTOMA

Novel Clinical Trial to Test TTFields with Radiation in Glioblastoma

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n innovative clinical trial evaluating a novel treatment device (TTFields) with radiation and chemotherapy for patients with glioblastoma is underway at SKCC. It is first in the world to offer this new treatment approach for patients with newly diagnosed glioblastoma.

Glioblastoma multiforme, or GBM, accounts for about half of primary malignant brain tumors in adults and is the most devastating. Conventional treatment consists of surgery, followed by radiotherapy and chemotherapy with a drug called temozolomide.

However, despite comprehensive multi-modality treatment, most patients’ cancers recur and they will die within two years. New therapeutic approaches are in urgent need.

A novel therapeutic device, TTFields (Optune), was recently FDA approved to treat GBM. TTFields has a unique mechanism of action. It generates low intensity, moderate frequency of wave-like alternating electric fields delivered directly to the tumor location through adhesive patches called tranducer arrays applied directly to the scalp. TTFields interferes with cell division, thus selectively targeting cancer cells, leading to cell death.

TTFields therapy is currently approved to treat both newly diagnosed and recurrent GBM. The most marked benefits were seen in patients with newly diagnosed GBM. The approval was based on a large, international phase III randomized trial that showed an improvement in overall survival of 4.9 months, an

increase of more than 30 percent.

Since the initial approval, substantial preclinical data have demonstrated a synergistic effect between TTFields and radiation treatment against the cancer cells, according to principal investigator Wenyin Shi, MD, PhD, co-director of the Brain Tumor Center and the Stereotactic Radiosurgery Program at SKCC. Radiation targets cancer cell DNA, resulting in unrepairable DNA double strand break and cell death.

TTFields disrupts cell division by inhibiting spindle fiber formation, thus disrupting proper chromosome separation, Shi explained. TTFields can also inhibit cancer cell proliferation, reduce DNA damage repair, and as a result, enhance the anti-cancer effects of radiation treatment.

These data led Shi and colleagues to develop the current clinical trial to evaluate treating patients with temozolomide, radiation, and TTFields concurrently. Radiation treatment will be delivered while the patient is wearing the device.

“Our group published the physics study that demonstrated the feasibility of delivering radiation through TTFields. We subsequently designed and opened the trial to test the novel

TTFields device

Wenyin Shi, MD, PhD Co-director, Brain Tumor Center and Stereotactic Radiosurgery Program

concurrent treatment in a clinical trial and are the first group internationally to treat GBM patients with radiation through TTFields arrays,” Shi said.

“We also developed novel ‘scalp sparing’ radiation techniques, which substantially reduce the radiation dose to the scalp as compared to conventional radiation techniques. This will reduce the side effects of concurrent use of radiation and TTFields.”

The trial is open and several patients have been successfully treated. The primary trial objective is to evaluate safety and toxicity of the combination chemoradiotherapy with the device treatment in newly diagnosed GBM. These findings will help the development of a phase III randomized trial evaluating the efficacy of this approach.  9

SKCC NEWS GASTROINTESTINAL CANCER

Meet the New Gastrointestinal Cancer Program Leader

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he Sidney Kimmel Cancer Center selected new leaders for two of its five NCI-designated research program areas. Jonathan Brody, PhD, Director of Surgical Research at Jefferson, is now head of the Gastrointestinal Cancer (GI) Program. He is be working alongside co-leader Scott Waldman, MD, PhD, Chair of the Department of Pharmacology & Experimental Therapeutics. Brody discussed his vision for the program and his own research on pancreatic cancer.

What is the overall aim of the Gastrointestinal Cancer Program?

In general, we have a multi-faceted approach to understanding the complexity of GI malignancies from studying basic molecular mechanisms of these cancers to translating these discoveries into improving existing therapies and developing novel therapies. Our ultimate aim is to enhance patient experience and outcomes with people who may be either diagnosed with a GI malignancy or may be at a high risk for getting one of these cancers. We are using sophisticated Patient Derived Models of Cancer to understand and target these cancers. We have multiple labs that are on the verge of testing their findings in different clinical settings.

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What do you hope to accomplish as program leader?

As a leader, I hope to facilitate connections between the strong clinical pillar and research community at Jefferson when it comes to diagnosing and treating GI cancers. We have such a great opportunity to link some of the best physicians from the fields of surgery, medical oncology, pathology, and radiation oncology with expert GI cancer-focused scientists. Ultimately by facilitating these connections, I believe that, through a multidisciplinary approach, we will positively change clinical practices and overall outcomes for patients with GI cancers.

What is your current research focus?

Currently, I am focused on studying pancreatic cancer, one of the most lethal of all cancers. I’ve been working on this complex problem for over 15 years.

My team is focused on many fronts.

First, we are trying to utilize all of our current genetic knowledge of this disease and gear it toward developing and optimizing a personalized therapeutic approach. For instance, we are part of a national movement to molecularly profile a patient’s tumor and match it to a specific therapeutic cocktail that will specifically kill the tumor. We are very interested in a subgroup of pancreatic

Jonathan Brody, PhD Director, Surgical Research

cancer patients who have a defect in their DNA repair machinery. Additionally, we are focused on a stress response pathway that pancreatic cancer cells hijack in order to stay alive under stressful conditions such as within the tumor neighborhood (where food is scarce) and the exposure to therapeutic treatments that apply stress to the tumor cell. We are currently setting up a clinical trial to target a key player (protein) in this pathway named HuR. In general, our mission is to further our understanding of why pancreatic cancer cells are so lethal on the molecular level and use this understanding to target it, as if it is an Achilles’ heel. 

SKCC NEWS PROSTATE CANCER

Meet the New Prostate Cancer Program Leader

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he Sidney Kimmel Cancer Center recently selected new leaders for two of its five research program areas.

Josep Domingo-Domenech, MD, PhD, Associate Professor of Medical Oncology and Cancer Biology, is now leading the Prostate Cancer Program. He is working alongside the program’s co-leaders, Alessandro Fatatis, MD, PhD, Professor of Pharmacology & Physiology at Drexel University, and Leonard Gomella, MD, Chair of the Department of Urology at Thomas Jefferson University and Clinical Director of the Sidney Kimmel Cancer Center Network. Domingo-Domenech shared his vision for the program and research currently underway in his own laboratory.

What is the overall aim of the Prostate Cancer Program?

The overall aim is to improve the quality of life and survival of prostate cancer patients. Although a great proportion of patients are diagnosed at early stages and cured with local therapies (surgery and/or radiation), there is a subset of patients who develop metastatic disease and will die because of cancer spread into vital organs. It is expected that in the United States more than 30,000 men will die from prostate cancer in 2019. The Prostate Cancer Program has a unique team of nationally and internationally recognized physicians and scientists who work together to offer the best treatment options and novel therapies. Efforts of the program

are focused on discovering basic fundamental mechanisms of disease progression, translating new biomarkers and therapeutic strategies to patients, and certifying that these new developments arrive to all of the population.

What do you hope to accomplish as program leader?

I plan to continue consolidating the program and enhancing collaborations among the outstanding members of the group to improve the management of prostate cancer patients. I look forward to further integrating clinicians’ and researchers’ interests within the program to enable rapid translation of projects from the bench to the bedside and vice versa, increasing the speed of implementation of novel discoveries into the clinic that will help prostate cancer patients.

What is your current research focus?

My particular research focus is to discover novel targetable mechanisms of aggressiveness in prostate cancer.

Our team use patient datasets and patient-derived experimental models to identify targetable mechanisms that boost lethal prostate cancer aggressiveness. These mechanisms are dissected using state-of-the-art molecular and

Josep Domingo-Domenech, MD, PhD Associate Professor, Medical Oncology and Cancer Biology

cancer biology techniques, which allow rigorous analysis of key molecules that can be pharmacologically targeted. The efficacy of novel therapeutic strategies are tested in preclinical models and set the rationale to develop early human clinical trials. Through this approach, our group has identified key molecules and signaling pathways (i.e. GATA2 IGF2 polykinase signaling network) that when inhibited significantly improve the efficacy of standard therapies. We expect that this and other therapeutic strategies we are developing will help improve prostate cancer patients’ survival in the near future. 

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NEW DEVELOPMENTS AWARDS AND HONORS ADAM BINDER, MD HemOnc Today Next Gen Innovator

CHRISTINE EISCHEN, PHD Distinguished Mentor Award Jefferson College of Life Sciences

SAVERI BHATTACHARYA, DO 2019 New Investigator Award Gynecologic Oncology Group Foundation

KAREN E KNUDSEN, MBA, PHD Elected to the American Association for Cancer Research Board of Directors

JONATHAN BRODY, PHD Permanent Member, Cancer Prevention Study Section, National Institutes of Health, Center for Science

AMY LEADER, PHD, MPH Elected to the College of Physicians of Philadelphia Section on Public Health and Preventative Medicine Executive Committee

STEVEN COHEN, MD Appointed to the American Society of Clinical Oncology-American Board of Internal Medicine Collaborative General Oncology Test Materials Development Subcommittee

CARIN GONSALVES, MD ROBERT ADAMO, MD DAVID ESCHELMAN, MD CURE Ocular Melanoma Vision of Hope Award Melanoma Research Foundation

ADAM DICKER, MD, PHD Fellow of the American Society of Clinical Oncology Care Delivery and Regulatory Policy Track Leader, 20192020 American Society of Clinical Oncology Annual Meeting Elected to the Society of Chairs of Academic Radiation Oncology Programs Executive Board

GRANTS DEPARTMENT OF MEDICAL ONCOLOGY AMERICAN CANCER SOCIETY Master’s Training Grant in Clinical Oncology Social Work

HIEN DANG, PHD AMERICAN LIVER FOUNDATION 2019 Charles Trey, MD Memorial Liver Scholar Award

EDITH P MITCHELL, MD GET YOUR REAR IN GEAR PHILADELPHIA Research Grant

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KUANG-YI WEN, PHD NATIONAL COMPREHENSIVE CANCER NETWORK ONCOLOGY RESEARCH PROGRAM and ELI LILLY AND COMPANY mChemoCoping – GC: A Text Messaging System Enabling Real-Time Monitoring and Management of Chemotherapy Side Effects Among Patients with Gastric Cancer (GC) NIH R01 A Mobile TXT-based Intervention to Improve Adherence to Adjuvant Hormone Therapy and Symptom Management for BCa Survivors BUCK CANCER FOUNDATION 2019 MEDICAL RESEARCH GRANT Tai Chi for Relieving Aromatase Inhibitor (AI)-induced Arthralgia in Breast Cancer Survivors

NEW DEVELOPMENTS DISCOVERIES OF NOTE Li Q, et al., Inhibition of Tissue-Nonspecific Alkaline Phosphatase Attenuates Ectopic Mineralization in the Abcc6 Mouse Model of PXE but Not in the Enpp1 Mutant Mouse Models of GACI. Journal of Investigative Dermatology. 2019 Feb; 139(2):360-368 Myers RE, et al., Decision Support and Navigation to Increase Colorectal Cancer Screening Among Hispanic Patients. Cancer Epidemiology, Biomarkers & Prevention. 2019 Feb; 28(2):384-391 Witherel CE, et al., Macrophage and Fibroblast Interactions in Biomaterial-Mediated Fibrosis. Advanced Healthcare Materials. 2019 Feb; 8(4):e1801451 Dowling JP, et al., TRADD regulates perinatal development and adulthood survival in mice lacking RIPK1 and RIPK3. Nature Communications. 2019 Feb 11; 10(1):705 Abraham TS, et al., TCR Retrogenic Mice as a Model To Map Self-Tolerance Mechanisms to the Cancer Mucosa Antigen GUCY2C. Journal of Immunology. 2019 Feb 15; 202(4):1301-1310 Tardif V, et al., Adenosine deaminase-1 delineates human follicular helper T cell function and is altered with HIV. Nature Communications. 2019 Feb 18; 10(1):823 Handley NR, et al., The Oncology Hospital at Home. Journal of Clinical Oncology. 2019 Feb 20; 37(6):448-452 Henderson NT, et al. Ephrin-B3 controls excitatory synapse density through cell-cell competition for EphBs. Elife. 2019 Feb 21; 8 Kolb AD, et al., Osteoblasts are “educated� by crosstalk with metastatic breast cancer cells in the bone tumor microenvironment.

Breast Cancer Research. 2019 Feb 27; 21(1):31 Abu-Khalaf M, et al., Breast cancer patients with brain metastasis undergoing GKRS. Breast Cancer. 2019 Mar; 26(2):147-153 Giri VN, et al., Germline genetic testing for inherited prostate cancer in practice: Implications for genetic testing, precision therapy, and cascade testing. The Prostate. 2019 Mar; 79(4):333-339 Mishra A, et al., MicroRNAs in Cutaneous T-Cell Lymphoma: The Future of Therapy. Journal of Investigative Dermatology. 2019 Mar; 139(3):528-534 Song A, et al., Phase I trial of alisertib with concurrent fractionated stereotactic re-irradiation for recurrent high grade gliomas. Radiotherapy and Oncology. 2019 Mar; 132:135-141

Dang H, et al., NELFE-Dependent MYC Signature Identifies a Unique Cancer Subtype in Hepatocellular Carcinoma. Scientific Reports. 2019 Mar 04; 9(1):3369 Zhang X, et al., RIPK1 can mediate apoptosis in addition to necroptosis during embryonic development. Cell Death & Disease. 2019 Mar 13; 10(3):245 Rhoades R, et al., Primary central nervous system plasmablastic lymphoma in an HIV-positive patient. BMJ Case Reports. 2019 Mar 14; 12(3) Wang CX, et al., The Post-Synaptic Function of Brca2. Scientific Reports. 2019 Mar 14; 9(1):4554 Debes GF, et al., Skin-Associated B Cells in Health and Inflammation. Journal of Immunology. 2019 Mar 15; 202(6):1659-1666 Hartsough EJ, et al., CADM1 is a TWIST1-regulated suppressor of invasion and survival. Cell Death & Disease. 2019 Mar 25; 10(4):281 Gennaro VJ, et al., Interaction between the BAG1S isoform and HSP70 mediates the stability of anti-apoptotic proteins and the survival of osteosarcoma cells expressing oncogenic MYC. BMC Cancer. 2019 Mar 22; 19(1):258 Piera-Velazquez S, et al., Endothelial to Mesenchymal Transition: Role in Physiology and in the Pathogenesis of Human Diseases.

Physiological Reviews. 2019 Apr 01; 99(2):1281-1324 Rogers C, et al., Gasdermin pores permeabilize mitochondria to augment caspase-3 activation during apoptosis and inflammasome activation. Nature Communications. 2019 Apr 11; 10(1):1689 Snook AE, et al., Split tolerance permits safe Ad5-GUCY2C-PADRE vaccine-induced T-cell responses in colon cancer patients. Journal for ImmunoTherapy of Cancer. 2019 Apr 23; 7(1):104 Johnson W, et al., Mogamulizumab versus investigator choice in relapsed/refractory adult T-cell leukemia/lymphoma: all four one or none for all? Haematologica. 2019 May; 104(5):864-867 Mohanty I, et al., Downregulation of thromboxane A2 and angiotensin II type 1 receptors associated with aging-related decrease in internal anal sphincter tone. Scientific Reports. 2019 May 01; 9(1):6759

13

FEATURE ARTICLE SURVIVORSHIP

Supportive Care for Cancer S

Treatment plans should also address p

T

hanks to recent advances in treatment, detection, and prevention, the number of cancer survivors continues to grow. The National Cancer Institute (NCI) estimated 15.5 million survivors were living in the United States in 2016 and that the number will increase over the next decade to 21.7 million.

would be a multifaceted approach to patient care that encompasses the myriad needs of each patient.

The Sidney Kimmel Cancer Center – Jefferson Health (SKCC) provides personalized care under its Cancer Care 360 model, which puts the patient in the center of a comprehensive

The NCI defines survivorship as beginning at the time of diagnosis until the end of one’s life. Survivorship is often thought of in three phases: from diagnosis through the initial treatment of the cancer, from the end of initial treatment through extended survival, and through longterm survivorship. There are different challenges associated with each phase, and of course, every patient is unique.

Immediately after receiving a cancer diagnosis, a patient’s first thoughts are understandably about immediate next steps for treatment.

This is when the medical, surgical, and radiation oncology teams begin working together to provide a personalized treatment plan.

However, cancer not only takes a physical toll on patients, but a psychosocial and economic one as well.

Research suggests that early integration of supportive care increases quality of life and improves outcomes for patients, so an ideal treatment plan 14

services that are available to patients from the time of diagnosis. “This can be anything from work and family-related issues, to the management of distress and other symptoms, education around survivorship-related topics, and guidance on nutrition, finances and insurance, sexuality and intimacy, and self-care,” Garber said.

circle of care surrounded by expert research, treatment, and supportive care. This approach, which combines precision medicine, promising research, and empowering services, is tailored to each patient to target the cancer and strengthen healing.

The Cancer Support and Welcome Center at SKCC provides patients with a centralized point-of-access to comprehensive care. An oncology social worker, Lisa Capparella, MSS, LCSW, OSW-C, manages the Welcome Center so visitors have immediate access to professional expertise in finding information on diagnosis, treatment, and support services. Located at 914 Chestnut Street, it can serve as a central arrival point for those being treated in Center City Philadelphia—patients can get help from staff on finding their way to appointments or stop in to relax in between appointments. Computer and internet access are available, as well as assistance with activating and using individual online medical charts.

Greg Garber, MSW, LCSW, is the Director of the Cancer Support and Welcome Center and Director of Patient Support Services at the Neu Center for Supportive Medicine and Cancer Survivorship. He leads teams that provide a variety of supportive and educational

Regularly available services at the Welcome Center include support groups; educational classes on cancer-related topics such as symptom management and medication side effects; gentle yoga classes; legal assistance; and the handling of can-

SKCC Cancer Care 360 Model

r Survivors Begins at Diagnosis

ss psychosocial needs of each patient cer-related fatigue, also available are support services that include fertility preservation and nutrition counseling.

Many of the educational classes are also available online for those who are not able to attend in person.

SKCC is also home to the Neu Center for Supportive Medicine and Cancer Survivorship, which provides holistic psychosocial cancer care to address the social, physical, emotional, financial, and spiritual needs of patients during the course of treatment and throughout the patient’s lifetime because it is important to heal the whole person, not just treat the cancer.

Pain and symptom management and individual and family counseling are among the many services available.

Additionally, there is a research component to the Neu Center. SKCC’s population scientists work closely with the supportive care team to evaluate the effects of psychosocial support intervention on stress, quality of life, resource use, cost, cancer outcomes, and the risk of treatment-related adverse effects. These findings will help establish best practices and set a new standard of care, helping patients at SKCC and beyond.

Once active treatment has fin-

“

ished, however, a patient still has unique physical and emotional health needs, and it is important to continue receiving care and support. Some survivors might be deemed “cancer free,” while others continue to live with their diagnosis for many years.

Some people may experience lateand long-term treatment effects.

Their healthcare needs and cancer screening requirements or risks for secondary cancers may have changed.

noses, and one way they can do that is through the Jefferson Buddy Program, which pairs current patients with volunteers who have gone through similar diagnoses (read the stories from survivors who now volunteer as “buddies” on pages 18 and 22).

Aggressively managing any physical or emotional symptoms is very important to help patients maximize their post-treatment functioning in as many areas as possible, Garber explained.

He and his team assess survivors after they finish active treatment to address any specific needs or concerns so that they can help with these needs or make the appropriate referrals.

The NCI notes that many caregivers put aside their own needs and feelings to focus on their loved one, but this is hard to maintain and physically and psychologically unhealthy.

“Depending on what a patient needs and their particular course of treatment, there are a variety of things we do from providing education about survivorship and end-of-treatment issues to assistance in addressing any issues that may impede adjustment after treatment,” he said.

Some people feel inspired to support others facing cancer diag-

Because a cancer diagnosis also affects those supporting the patient, it is important for families and caregivers to seek out support and care for themselves as well.

“Caring for family and caregivers is critical to the support we provide, and we offer a variety of programs through the Welcome Center,” Garber said.

These offerings include support groups for caregivers, mindfulness seminars, and Reiki and massage therapy.

For more information about the supportive services available to patients and caregivers, contact the SKCC Cancer Support and Welcome Center at 215-955-1800 or CancerSupportCenter@jefferson.edu, or the Neu Center for Supportive Medicine and Cancer Survivorship at 215-955-1888. 

Do you have any advice to offer someone who has just received a cancer diagnosis?

Receiving a cancer diagnosis is often an overwhelming experience for patients and those close to them. There are many unanswered questions and high levels of distress. I typically suggest that people find an oncology provider they trust and feel comfortable with and seek information from reliable, evidence-based resources rather than doing internet searches. Distress tends to lessen once a course of action is determined, but if it remains elevated, it is worth seeking out a social worker or other helping professional.

“

- Greg Garber, MSW, LCSW 15

CLINICAL TRIAL LYMPHOMA

Epigenetic Therapy Shows Effectiveness in Epstein-Barr Virus-associated Lymphomas

A

combination of nanatinostat (VRx3996), an oral histone deacetylase (HDAC) inhibitor, and the oral antiviral valganciclovir appeared to be well tolerated and had efficacy in patients with Epstein-Barr Virus (EBV)-associated lymphomas, according to data from a phase Ib/II study.

Pierluigi Porcu, MD, Director, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation at SKCC and global study lead, presented the data at the American Society of Clinical Oncology Annual Meeting (ASCO).

“One of the most important findings so far is the determination of a well-tolerated dose for the combination of nanatinostat and valganciclovir in patients and we are pleased to have seen such promising responses thus far,” Porcu said. “The main purpose of this study was to develop a new treatment strategy for EBV-associated lymphomas that takes advantage of the vulnerabilities imposed on the cancer by the presence of the virus and I am excited to see the combination advance into further clinical studies.”

This combination of nanatinostat and valganciclovir is a new form of therapy for EBV-associated lymphomas that targets the virus itself. It is an epigenetic approach, which modifies the interactions between the virus, the tumor cell, and the microenvironment and stimulates immune responses while activating the expression of certain viral proteins so that the tumor becomes more sensitive to antiviral drugs.

EBV is a member of the herpesvirus

16

family, primarily infecting white blood cells known as B lymphocytes, or B cells. It is one of the most common human viruses, infecting most people at some point in their lives. EBV is best known as a cause of mononucleosis, although many people who contract it are asymptomatic. Like other herpes viruses, EBV remains latent in the body after infection. Although carrying EBV does not cause problems for most people, it can increase the risk of some cancers, including Hodgkin and non-Hodgkin lymphomas.

The study evaluated three doses of the combination of nanatinostat with valganciclovir. Both drugs are taken orally and can be given on an outpatient basis. Responses were observed across all doses, and in B- and T-cell lymphoma subtypes, including Hodgkin lymphoma.

The overall objective response rate of 58 percent, complete response rate of 33 percent, and disease stabilization rate of 75 percent is encouraging, and warrants advancement to the phase II stage of the study, according to Porcu.

The combination was well tolerated with no unexpected toxicity. The most

Dr. Porcu presenting his findings at ASCO

Pierluigi Porcu, MD Professor, Medical Oncology Director, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation

common adverse events were hematologic, easily managed, and resolved without sequelae or bleeding events. A cohort evaluating intermittent dosing of nanatinostat in combination with daily valganciclovir is being evaluated as the recommended phase 2 dose.

The FDA granted orphan drug designation to nanatinostat, which is being developed by Viracta Therapeutics, Inc., in combination with valganciclovir for the treatment of EBV-associated cancers. The FDA grants orphan drug designation to drugs and biologics intended to treat, diagnose, or prevent rare diseases/disorders that affect fewer than 200,000 people in the U.S., or that affect more than 200,000 people but are not expected to recover development and marketing costs. 

BREAKTHROUGH PROSTATE CANCER

Bench-to-Bedside Study of a Targetable Enzyme Controlling Aggressive Prostate Cancer

A

new study led by investigators at the Sidney Kimmel Cancer Center – Jefferson Health (SKCC) has revealed a key cellular mechanism that contributes to aggressive prostate cancer, supporting a new clinical trial of a novel inhibitor drug.

The SKCC researchers and their collaborators at Memorial Sloan Kettering Cancer Center, University of California, San Francisco (UCSF), and Celgene Corporation focused on the enzyme DNA-PK (DNA-dependent protein kinase), a pivotal component of the cellular machinery that controls both DNA repair and influences gene expression.

The study, which was published in Clinical Cancer Research, was orchestrated from the laboratory of Karen E. Knudsen, MBA, PhD, EVP of Oncology Services and Enterprise Director of SKCC. Previous studies showed that DNA-PK is excessively active in metastatic prostate cancer and that its hyperactivation is associated with a poor outcome in prostate cancer patients. “Our study further elucidates the functions of DNA-PK and identifies this protein as a master regulator of gene networks that promote aggressive cancer behaviors,” said lead author Emanuela Dylgjeri, a doctoral candidate in the Knudsen laboratory.

A companion study led by Felix Feng, MD, of UCSF, in collaboration with the Knudsen laboratory, identified DNA-PK as the most significantly associated kinase with metastatic progression of the disease. In an effort

to understand how DNA-PK induces poor outcomes, the investigators found that DNA-PK modulates the expression of gene networks controlling a variety of important cancer-related cellular events, including a developmental process termed the epithelial-mesenchymal transition, the immune response, metabolic pathways, and Wnt signaling.

“It is our hope to use the information gained by these studies to understand which prostate cancer patients might benefit the most from combination treatments with a DNA-PK inhibitor drug.”

The new findings suggest that targeting DNA-PK might allow the development of effective strategies to prevent or treat aggressive, late-stage prostate cancer. Data from the studies were used to develop a clinical trial combining standard-of-care with a first-in-human DNA-PK inhibitor. Early trial results have been promising, and the researchers have demonstrated in a laboratory setting that the combined approach is more effective than either single treatment in eliciting anti-tumor effects. The clinical trial is still underway and has now entered the expansion phase of testing.

The new studies focused on translating basic science findings from the laboratory to the clinic, but the investigators also plan to take the lessons learned in the clinic back to the laboratory. The results of the clinical trial will offer important clues and raise new questions that will guide the design of

Karen E. Knudsen, MBA, PhD Executive Vice President Oncology Services Enterprise Director Sidney Kimmel Cancer Center

new experiments, with the ultimate goal of understanding how DNA-PK regulates specific cellular pathways to promote more aggressive cancer behavior. These studies in turn will aid in the development of more accurate genetic tests to detect advanced prostate cancer, identify the most appropriate course of treatment for individual patients, and predict treatment outcomes.

Knudsen envisions long-term practical outcomes of this research. “It is our hope to use the information gained by these studies to understand which prostate cancer patients might benefit the most from combination treatments with a DNA-PK inhibitor drug.” 

17

SURVIVOR STORIES LOU LANZA & JOHN BUEHLER

Survivors Offer Support to Others Facing Cancer

L

ou Lanza, a mechanical engineer from Philadelphia, has unfortunately been surrounded by cancer his entire adult life. His mother and sister both succumbed to the disease, as well as several friends. In 2005 cancer struck once again, and this time, Lanza himself was the patient. He was diagnosed with stage II non-Hodgkin lymphoma after a mass was discovered in his chest. Now in remission, he often recounts his long, challenging cancer journey and encourages others to seek support wherever possible.

Advocacy and volunteering have been integral to Lanza’s life as a cancer survivor. In the decade since his diagnosis, he has become a patient advocate for organizations including the American Association for Cancer Research and the American Society of Clinical Oncology. His dedication to the fight against cancer earned him a 2018 Man of the Year award from South Jersey Magazine.

Lanza also gives back to SKCC through various volunteer opportunities. As a Jefferson “Buddy on the Spot,” he spends time with patients in the midst of chemotherapy treatment.

He explains that he always “aims to find the sweet spot” with every person he meets — food, sports, family — whatever will help distract them and make them comfortable during a difficult time. “My advice to any cancer patient is to always talk to others — don’t hold anything in,” he said.

When Warrington, Pa. native John Buehler was diagnosed with stage III

18

prostate cancer in 2008, he had a lot of questions but felt he didn’t have a lot of people to talk to except his wife and a few family members.

When Buehler was in the hospital recovering from his cancer-related surgery, his roommate struck John Buehler (left), with Lou Lanza up a conversation as a way to help In 2017, Buehler attended the distract Buehler Philadelphia Prostate Cancer Confrom his pain and discomfort. The sensus, an international meeting roommate, who also had cancer, told co-sponsored by Thomas Jefferson Buehler that he hadn’t told any of his University and the Foundation for friends about his diagnosis. Buehler Breast and Prostate Health that was decided he didn’t want to stay quiet about his own situation ion the chance held on Jefferson’s campus. While there, a meeting attendee recognized that his story could help save lives.

Buehler. “He told me, ‘John, when I “You might think you’re on this think of you, I think of prostate cancer,’ rock by yourself, but you’re which I took as a huge compliment,” not... I personally got through Buehler recalled. “I truly believe that my cancer treatment thanks to my Jefferson team and a vast I was spared to be able to help other amount of family and friends.” people and to be a voice for others.”

After successfully going into remission, Buehler, president and co-owner of F.E. Buehler & Son, Inc., a fourth-generation well-drilling firm, made it his mission to share his story with others whenever possible, especially with the men in his professional and social circles, who can be reluctant to share personal stories. “Most people like my honest life experiences,” he explained.

Lanza and Buehler have also become friends through their involvement in the SKCC community, and they both credit their various networks for support as they continue on their own survivorship journeys. “You might think you’re on this rock by yourself, but you’re not,” Lanza said. “I personally got through my cancer treatment thanks to my Jefferson team and a vast amount of family and friends.” 

ACCOL ADES LEADING BY EXAMPLE

Dr. Adam Dicker Named ASCO Fellow

A

dam P. Dicker, MD, PhD, has been named a Fellow of the American Society of Clinical Oncology (FASCO) in honor of his extraordinary volunteer service, dedication, and commitment to ASCO. Dicker is Senior Vice President and Chair of Enterprise Radiation Oncology; Director of the Jefferson Institute for Digital Health; and Professor of Radiation Oncology and Pharmacology and Experimental Therapeutics at the Sidney Kimmel Cancer Center – Jefferson Health (SKCC).

The FASCO title is bestowed upon members who have carried out efforts that benefit ASCO, the specialty of

oncology, and the patients they serve.

Dicker is a leading expert in prostate cancer and brain tumors with a focus on digital health and translational sciences applied to oncology. His team of oncologists, immunologists, physicists, data scientists, nurses, and behavioral scientists work in a multidisciplinary manner to define mechanisms and targets for cancer treatment and translate them to effective innovations for patients. As Director of the Jefferson Institute for Digital Health, he leads a university-wide effort in digital health and data science using the convergence of mobile technology, platforms, networks, and machine learning to improve the lives of patients. 

Adam Dicker, MD, PhD SVP and Chair, Enterprise Radiation Oncology Director, Jefferson Institute for Digital Health

Dr. Neal Flomenberg Receives Inaugural Lifetime Achievement Award from LLS of Eastern Pa.

N

eal Flomenberg, MD, Enterprise Deputy Director of the Sidney Kimmel Cancer Center – Jefferson Health (SKCC) was honored with the inaugural Rudolph and Antoinette Roesler de Villiers’ Lifetime Achievement Award from the Leukemia & Lymphoma Society (LLS) – Eastern Pennsylvania Chapter.

Dr. Flomenberg (left) accepts his award from Dr. Louis J. DeGennaro, President and CEO of the Leukemia & Lymphoma Society

The award honors scientific researchers who are making extraordinary differences in the fight against blood cancers. Flomenberg, who is also Professor and Chair of the Department of Medical Oncology and Director of the Blood and Marrow Transplant Program at SKCC, was recognized at the annual LLS Red & White Ball.

Flomenberg’s clinical and laboratory career has focused on the immunobiology of allogenic hematopoietic stem cell transplantation, with the goal of making transplantation safer and more widely available to patients. His current transplant approaches are unique and designed to enfranchise patient populations lacking well-matched donors as well as serving fit, senior adults.

He has received numerous other honors throughout his career, including the LLS Lifetime Award for Contributions to Mankind, Thomas Jefferson University’s Simon Gratz Award for research most likely to influence patient care, and Penn State University’s Outstanding Science Alumni Award.  19

B REAKTHROUGH POPULATION HEALTH

Pre-existing CVD Associated with Higher Mortality After Starting Abiraterone Acetate for Prostate Cancer study was to provide clinical outcomes for patients who did not meet the eligibility criteria for the trial and to determine whether the benefits reported in the pivotal trials could also be applied to these patients, Lu-Yao explained.

Grace Lu-Yao, PhD, MPH Associate Director Population Science Professor, Medical Oncology Division of Population Science

M

en with pre-existing cardiovascular disease (CVD) had a higher risk of mortality within six months of starting abiraterone acetate (Zytiga), an androgen deprivation therapy for advanced prostate cancer, compared with patients who had no pre-existing CVD, according to research from Grace Lu-Yao, PhD, MPH, Associate Director of Population Science at the Sidney Kimmel Cancer Center – Jefferson Health (SKCC).

Patients with pre-existing CVDs and uncontrolled hypertension were often excluded from abiraterone acetate clinical trials, which means the trial results might not be generalized to patients in the real-world setting since these conditions are very common in the general population. The main purpose of this

20

“The overall risk/benefit ratios observed in the clinical trial might be very different from those with pre-existing conditions in the real-world setting. It is critical to make sure that the benefits of medication outweigh potential risks in the real-world setting,” said Lu-Yao, who presented her findings during an oral session of the American Association for Cancer Research (AACR) Annual Meeting 2019. This is the largest population-based study to examine clinical outcomes of patients in the US who are unlikely to be eligible for clinical trials of abiraterone acetate.

Using data from the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database, Lu-Yao and colleagues examined 2,845 prostate cancer patients diagnosed between 1991 and 2013 and treated with abiraterone acetate from 2011 to 2014. They found that 1,924 patients (67.6 percent) had at least one pre-existing cardiovascular condition prior to treatment, such as acute myocardial infarction, congestive heart failure, atrial fibrillation, stroke, or ischemic heart disease.

Among patients with pre-existing CVD, the crude risk of overall mortality within six months ranged from 21.4 percent among men with ischemic heart disease to 25.6 percent among those with acute myocardial

infarction compared with 15.8 percent for men with no pre-existing CVD. “The results shown in the clinical trials are more favorable than the results experienced by the general population,” Lu-Yao explained. “Patients with existing CVD experienced higher mortality, mainly in the first six months of the drug initiation.”

The researchers also found an increased risk of hospitalization within six months of starting abiraterone acetate among all patients, regardless of CVD status. Among those without pre-existing CVD in the pre-chemotherapy setting, the six-month post-treatment hospitalization rate increased 53 percent compared with the hospitalization rate in the six-months before treatment. The hospitalization rate increase ranged from 34 percent in men with atrial fibrillation to 55 percent in those with acute myocardial infarction.

Abiraterone acetate was FDA-approved in 2011 to treat metastatic castration-resistant prostate cancer in combination with prednisone. In 2018, it was approved in high-risk metastatic castration-sensitive prostate cancer.

As the drug indication approved for an earlier disease setting, it becomes even more important to understand its potential treatment-related adverse effects and weigh the risk/benefit carefully.

“Most cancer therapies have side effects and the risk/benefit ratio may vary based on the health status of the patient,” Lu-Yao said. “The health status and the medication’s potential effects on survivorship need to be considered when making treatment decisions.” 

BREAKTHROUGH GLIOBLASTOMA

Clinical Trial Shows Promising Results for Novel Glioblastoma Vaccine

A

n investigational vaccine for glioblastoma multiforme developed by Jefferson and Imvax, Inc. was well tolerated and improved progression-free and overall survival, according to results from a phase Ib clinical trial.

Researchers treated 33 patients with newly diagnosed glioblastoma with the vaccine (IGV-001) and compared outcomes to a historical comparator group of 35 patients treated with the standard of care alone. They divided the patients into four groups treated at various vaccine doses and found the median overall survival for patients treated with the highest dose of the vaccine was 21.9 months, compared with 14.6 months for standard of care. Median progression-free survival was 10.4 months for the highest vaccine dose, compared with 6.9 and 5.4 months in published standard-of-care studies.

“The response we see in some patients is very encouraging,” said David Andrews, MD, Professor of Neurosurgery at the Vickie & Jack Farber Institute for Neuroscience – Jefferson Health and co-founder, Chief Medical Officer, and interim CEO of Imvax. “We look forward to initiating a phase II trial later this year to confirm these phase 1b results.”

Andrews presented the data at the American Association for Cancer Research Annual Meeting 2019.

The vaccine is created from the patient’s own tumor cells sampled during surgical removal of the primary brain tumor. Researchers take the

cells, treat them with an antisense oligodeoxynucleotide (AS-ODN) against IGF-1R, a receptor shown to drive tumor growth and metastasis, and load them with additional AS-ODN into diffusion chambers. The dimesized chambers and their contents are irradiated and implanted under the skin of the patient’s abdomen.

“As a consequence of the combined effects of the IGF-1R antisense and irradiation, our evidence shows that the chambered tumor cells release antigens, which together with the immunomodulatory AS-ODN, diffuse out of the chamber into the patient’s body and activate the immune system against brain tumor cells,” said D. Craig Hooper, PhD, Professor of Cancer Biology at Sidney Kimmel Cancer Center and co-founder and Chief Scientific Officer of Imvax.

Andrews was interested in using antisense molecules that render glioblastoma cells more susceptible to conventional radiotherapy. However, preclinical experiments and an early clinical study of the effect of implantation of diffusion chambers containing glioblastoma cells showed there was radiographic evidence of delayed tumor shrinkage, which suggested that a systemic, possibly immune response might be at play. To better understand the observations, Andrews reached out

David Andrews, MD Professor, Neurosurgery Vickie & Jack Farber Institute for Neuroscience

to Hooper, who has an extensive background studying immune regulation and expertise in neuroimmunity. Over the course of 15 years, their translational research and clinical studies refined the diffusion chamber combination product used in the current trial.

“This is an incredibly important advance emerging from leading investigators from the Sidney Kimmel Cancer Center. We are enthusiastic about the potential for this intervention, and as is befitting for an NCI-designated cancer center, we are proud to have provided the initial seed funds to develop the bold new idea,” said Karen E. Knudsen, MBA, PhD, EVP of Oncology Services and Enterprise Director of SKCC. 

21

SURVIVOR STORY ARLEEN WEITZ

After Cancer, A Survivor Looks on the Bright Side for saving her life. Through Rehm and DiMaria, she decided to become a Buddy in order to help other patients navigate the challenges of cancer treatment. She volunteers at the TJUH Center City Oncology Infusion Center, where she provides comfort to patients receiving chemotherapy infusions.

Cancer survivor Arleen Weitz (right) with her Jefferson Cancer Buddy, Carmela DiMaria

A

rleen Weitz, an event planner from Philadelphia, has always been what she describes as a “glass-half-full kind of person.” So when she suddenly began experiencing rectal bleeding at the end of 2012, she hoped for the best — either a broken blood vessel or hemorrhoids. However, when Weitz’s Jefferson primary care physician Matthew Killion, MD, examined her, he expressed his concerns and coordinated an expedited consult with Scott Goldstein, MD, Director of the Division of Colon and Rectal Surgery.

Less than 24 hours later Weitz received a colonoscopy, and the results were much more serious than expected: the medical team suspected cancer. In February 2013, Weitz underwent laparoscopic surgery for a colon resection performed by Gold-

22

She also volunteers at the SKCC Cancer Support and Welcome Center.

“Arleen is very involved in the success and growth of the Welcome Center, where she will offer a helping hand and meet with newly diagnosed patients to provide empathy and support.

She is an invaluable volunteer who impacts everyone around her,” said Lisa Capparella, MSS, LCSW, OSW-C,

“It’s been the silver lining of my illness. Had I not had cancer, I wouldn’t have had the opportunity to meet so many people who have affected my life in such a positive way.”

stein, which is when she was officially diagnosed with stage III colorectal cancer. She then underwent 12 weeks of chemotherapy under the supervision of Andrew Chapman, DO, Chief of Cancer Services at the Sidney Kimmel Cancer Center (SKCC).

Manager of the Welcome Center.

While undergoing chemotherapy, Weitz was introduced to Kate Rehm, MSW, LCSW, Director of the Jefferson Buddy Program. The Buddy Program pairs newly diagnosed cancer patients with volunteers who have gone through a similar diagnosis. Weitz was matched with a colorectal cancer survivor named Carmela DiMaria, who has continually supported Weitz throughout her treatment and survivorship journey.

At Weitz’s five-year follow-up appointment in 2018, her scans luckily showed no evidence of disease.

Through it all, her positive outlook has never changed. “Despite all the challenges of my illness, I have met so many wonderful people at Jefferson.

It’s been the silver lining of my illness,” she reflected. “Had I not had cancer, I wouldn’t have had the opportunity to meet so many people who have affected my life in such a positive way.” 

After her recovery, Weitz wanted to give back to the hospital she credits

WELCOME CENTER CLIMB PROGRAM

Children and Teens Offered Psychosocial Support through CLIMB Program

W

hen a person is diagnosed with cancer, the entire family is affected. Children and teenagers in particular might have difficulty expressing their feelings about the situation. The SKCC Cancer Support and Welcome Center now offers CLIMB® (Children’s Lives Include Moments of Bravery), a free support program developed by the Children’s Treehouse Foundation for younger people who have a parent or grandparent with cancer.

The program, now offered twice yearly at the Welcome Center, meets for six consecutive weeks. Each week, families share a meal together and then break off into groups of school-age children (ages 6-12), teens (ages 13-17), and parents. Licensed social workers facilitate all groups.

Through art projects, games, and group discussions, CLIMB helps children, teens, and their parents understand the complex feelings that can go along with having a family member diagnosed with cancer. Children and teens will learn that feelings such as concern, sadness, anger, and happiness are all expected and that it can help to talk, write, or draw about their feelings rather than keep them inside.

Most importantly, they can discover that they are not alone — there are other young people out there who can relate to their experiences.

To learn more about CLIMB, contact the Cancer Support and Welcome Center at 215-955-1800 or email CancerSupportCenter@jefferson.edu. 

A mask created during the CLIMB Program

“She looked forward to the group each week. She enjoyed getting to know other children going through the same thing and being allowed to express herself to people who really understood.”

-From a parent of a 7-year-old

“The most helpful part was sharing our experiences with other parents and finding our bonds.”

-From a parent of a 17-year-old

“The best part of the program was meeting new people who are in situations close to mine.”

-From a 16-year-old

“The best part was doing art. Thanks!”

-From a 9-year-old

Children work on art projects to help process their feelings in the CLIMB Program

23

ASPLUNDH NEWS FROM THE NORTH

New Therapy for Neuroendocrine Tumors Available at SKCC-Abington treatment option available to them— lutetium Lu 177 dotatate (Lutathera).

Lutathera works by binding to the somatostatin receptors on the surface of the tumor cells while the radioactive substance, Lu 177, delivers high-dose radiotherapy to kill the tumor cells throughout the body. A phase III clinical trial had demonstrated a 79 percent reduction of disease progression or death among patients receiving Lutathera and octreotide compared with patients who received octreotide alone, which had been the standard of care. The researchers found the median progression-free survival was almost three years among the patients receiving Lutathera.

Rajan Agarwal, MD Medical Director, Nuclear Medicine and PET Imaging Asplundh Cancer Pavilion

P

atients with somatostatin receptor-positive neuroendocrine tumors (NETs) being treated at the Sidney Kimmel Cancer Center at Abington-Jefferson Health have a new

“I am proud to say that our amazing team can now provide this novel therapy to our local and regional community.”

“The management of patients with neuroendocrine tumors is difficult. NETs of the midgut are the most common type of GI NETs and are

associated with a five-year survival rate of less than 50 percent among people with metastatic disease,” said Rajan Agarwal, MD, Medical Director of Nuclear Medicine and PET Imaging at Abington-Jefferson Health. “The data from the trial are remarkable; it is not often that a new oncologic therapy results in a 79 percent reduction of disease progression or death.”

When the FDA approved Lutathera in the United States in 2018, Agarwal and his team worked quickly to build this complex therapy program, which treated its first patient in December 2018.

“I am proud to say that our amazing team can now provide this novel therapy to our local and regional community. At SKCC-Abington we strive to keep our radiology department at the cutting edge of medicine so we can provide our patients and our community with the latest and the greatest care in a friendly, safe, and high-quality manner,” Agarwal said. 

Sidney Kimmel Cancer Center - Asplundh Cancer Pavilion

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WASHINGTON TOWNSHIP NEWS FROM NEW JERSEY

SKCC Expanding Comprehensive Cancer Services in South Jersey

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he Sidney Kimmel Cancer Center – Washington Township continues to expand its medical oncology program to offer patients in South Jersey access to cancer care close to home.

The program offers a comprehensive range of services, including genetic counseling, leading-edge treatment options, and supportive care, in addition to a new medical oncology infusion suite that features infusion bays and an onsite pharmacy and laboratory.

“SKCC through Jefferson Health – New Jersey is bringing state-ofthe-art, coordinated, team-based cancer care to the region to provide whole-person compassionate care across the cancer treatment spectrum,” said Ana María López, MD, MPH, Professor and Vice Chair of Medical Oncology, and Chief of Cancer Services at the Sidney Kimmel Cancer Center – Washington Township.

Cancer represents a set of illnesses that affect the patient, the family, and the community in multiple ways, López explained. SKCC – Washington Township seeks to care for the patient in context, acknowledging the physical, emotional, nutritional, and other psychosocial aspects of care. A coordinated team of experts, including medical oncologists, clinical nurses, and nurse navigators, provide personalized care.

“Cancer treatment no longer takes place within the silo of any one specialty. Cancer treatment is the epitome not only of multidisciplinary care but also of translational care,” López said. “This combined effort brings the right care and the right treatment to the patient. This team-based approach illustrates our emphasis on your wellness and healing.”

Additionally, SKCC – Washington Township is addressing access to care through telemedicine and by expanding the clinical trials available to patients.

“SKCC – Washington Township emphasizes the cancer care spectrum, as we are as committed to prevention as we are to treatment and supportive care” “Cancer prevention and treatment are rapidly evolving through advances in science, which take place through cancer clinical trials. By bringing cancer clinical trials to our community—trials that have our community in mind—the Sidney Kimmel Cancer Center – Washington Township seeks to improve cancer outcomes from prevention to palliation,” López said.

“We are pleased to work with an established community of primary

Ana María López, MD, MPH Vice Chair, Medical Oncology Chief of Cancer Services, SKCC Jefferson Health-New Jersey

care, specialty care, and subspecialty care colleagues and to meet the cancer needs of our community,” López said. “Most places emphasize the therapeutic aspect of care. SKCC – Washington Township emphasizes the cancer care spectrum, as we are as committed to prevention as we are to treatment and supportive care. All are areas where we can work together to improve the care of our community.”

For more information on the Sidney Kimmel Cancer Center – Washington Township, call 856-557-7900. 

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PHIL ANTHROPIC SUPPORT EVENTS

Get Your Rear in Gear Philadelphia

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nspired by the loss of her father and grandfather to colorectal cancer, Maria Grasso started Get Your Rear in Gear Philadelphia, a Colon Cancer Coalition event, 11 years ago. Get Your Rear in Gear Philadelphia is a four-mile run, two-mile walk, and kids’ fun run held each March, which is National Colorectal Cancer Awareness Month, and is Greater Philadelphia’s largest colon cancer awareness event. With the support of patients, families, and friends, $550,000 has been directed to Sidney Kimmel Cancer Center (SKCC) and Jefferson Health for their efforts in colorectal cancer awareness, screening, and research. 

Maria Grasso (left), Executive Director of Get Your Rear in Gear Philadelphia, presents Dr. Edith P. Mitchell with a $25,000 check. SKCC received $85,000 from the Colon Cancer Coalition from this year’s event.

Preserving the Love

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from left – Janet Doherty, Dr. Jason Franasiak, Howard Eskin— who was honored with the Geraldine Hunter Preserving the Love Award for his support of the fund—and Ian Doherty.

n May 11, Janet and Ian Doherty celebrated the fifth annual Preserving the Love’s Night Out on the Town to support research at SKCC to improve fertility preservation outcomes for cancer patients. Janet Doherty founded Preserving the Love after undergoing successful treatment for breast cancer, which she was diagnosed with at the age of 30. More than 250 guests attended the successful event, during which Jason M. Franasiak, MD, Lead Physician at Reproductive Medicine Associates of New Jersey in Marlton, N.J., and Assistant Professor in the Division of Reproductive Endocrinology and Infertility at Thomas Jefferson University, provided an update on research the event has been supporting over the years. 

To learn more about the many ways a gift today can have a significant impact on cancer breakthroughs, please contact the Office of Institutional Advancement at 215-503-7604.

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PHIL ANTHROPIC SUPPORT EVENTS

Annual SKCC Men’s Health Event

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he Sidney Kimmel Cancer Center – Jefferson Health (SKCC) held its second annual Men’s Health Event at the Prime Rib in Center City Philadelphia. The event supports prostate cancer research at SKCC. This event was hosted by Leonard G. Gomella, MD, Bernard W. Godwin, Jr. Professor of Prostate Cancer; Chair, Department of Urology; Senior Director, Clinical Affairs at SKCC; and Clinical Director, Sidney Kimmel Cancer Center Network; and Karen E. Knudsen, MBA, PhD, Executive Vice President of Oncology Services and Enterprise Director of SKCC. SKCC Advisory Council members Kent Gushner and Joe Weiss again served as honorary co-chairs.

“Our 2019 Men’s Event was an outstanding gathering of clinicians, investigators, patients, and supporters that validated the reason we work every day at the SKCC,” Gomella said. “The program was not all serious cancer business, however. It included great comedic entertainment and the camaraderie of every lady and gentleman who shared the terrific evening with us.” 

Actor and comedian Kevin Pollack entertains the sold-out crowd with his standup routine

Gregory Kane (left) and friends enjoy dinner at the Prime Rib

Sidney Kimmel Cancer Center’s prostate cancer leadership. Clockwise, from left: Drs. Leonard Gomella, Wm. Kevin Kelly, Alessandro Fatatis, Josep Domingo-Domenech, Adam Dicker, Karen Knudsen

An evening of charity gaming supports leadingedge prostate cancer research 27

233 South 10th Street Bluemle Building Room 1050 Philadelphia, PA 19107

UPCOMING EVENTS SEPTEMBER Strike Out Cancer Night 27 Phillies Citizens Bank Park 7:05pm

OCTOBER Prostate Cancer Consensus 4 Philadelphia Conference October 4 & 5, Hamilton Building 1001 Locust Street

Breast Cancer and Related Diseases 19 Annual Symposium Hamilton Building 1001 Locust Street

NOVEMBER Annual Pancreatic Cancer and Related 16 14th Diseases Patient Symposium Hamilton Building 1001 Locust Street

FOR MORE INFORMATION VISIT SIDNEYKIMMELCANCERCENTER.ORG