Dr. Gomella, Associate Director for Clinical Affairs Appointed to NCI Genitourinary Cancers Steering Committee

Dr. Leonard Gomella

Dr. Leonard Gomella

Dr. Leonard Gomella, Chairman of the Department of Urology and Associate Director for Clinical Affairs for the Sidney Kimmel Cancer at Jefferson has been appointed to serve on the NCI Genitourinary Cancers Steering Committee (GUSC). The GUSC is one of sixteen steering committees formed to leverage current NCI-supported NCTN Groups, Consortia, SPOREs and Cancer Center structures to design and prioritize national cancer related clinical trials. The GUSC charge is to prioritize and review concepts for phase 2 and phase 3 clinical trials and provide a forum for critical review of concepts for new trials by a broad spectrum of experts from across the NCI-supported clinical trials enterprise and from international partners.

Dr. Gomella, one of the founding members of the Sidney Kimmel Cancer Center, also serves as Clinical Director for the Jefferson Sidney Kimmel Cancer Network and as Urology Chair for NRG, formerly the Radiation Therapy Oncology Group. In addition to being recognized as an outstanding clinician in regional and national “Top Doctor” listings, he is involved in translational basic science and clinical research in the development of new diagnostic techniques and treatments for prostate, bladder and kidney cancer.



Dr. Gomella elected to the Clinical Society of Genitourinary Surgeons

Dr. Leonard Gomella

Dr. Leonard Gomella

Leonard G. Gomella, MD, The Bernard W. Godwin Professor of Prostate Cancer, Chairman, Department of Urology, Associate Director, Jefferson Kimmel Cancer Center, Clinical Director Jefferson Kimmel Cancer Center Network, Editor-in-Chief, Canadian Journal of Urology has been elected to the Clinical Society of Genitourinary Surgeons. This is considered one of the most prestigious societies in the field with active membership limited to 25 of the top academic urologists in the US.



Jefferon’s Kimmel Cancer Center Holds 5th Annual Men’s Event

Jefferson’s Kimmel Cancer Center hosted its 5th Annual Men’s Event to benefit prostate cancer research and awareness at the Prime Rib Restaurant on November 14.

Below are some photos of the night, award ceremony and entertainment provided by Comedy Central’s “100 Greatest Stand-Ups of All Time,” Jim Breuer of Saturday Night Live.


“Spirit of Caring” Awardee:

Wm. Kevin Kelly, D.O.

Professor, Medical Oncology and Urology,
Director, Division of Solid Tumor Oncology

The “Spirit of Caring Award” is presented to an individual to recognize outstanding leadership in cancer research and the hope they hold for improving the quality of life in every community.

“Spirit of Courage” Awardee:
Anthony DiPrimio, PhD

Author, Prostate Cancer: What Men Need to Know About this Disease and Its Treatment

The “Spirit of Courage Award” is presented to an individual who has demonstrated great personal courage, strength and dignity while battling cancer and supporting others in their fight against cancer.

“Spirit of Commitment” Awardee:
Neal Rodin

President, International Financial Company, LLC

The “Spirit of Commitment Award” is presented to an individual to recognize outstanding commitment to supporting the work of the Kimmel Cancer Center through personal and professional contributions dedicated to finding a cure.

“Spirit of Innovation” Awardee:
Dendreon:
The company applies its expertise in antigen identification, engineering and cell processing to produce active cellular immunotherapy (ACI) product candidates designed to stimulate an immune response. They pioneered a novel, first in class autologous immunotherapy first approved for the treatment of advanced prostate cancer. Dendreon is headquartered in Seattle with corporate operations based locally in the Delaware Valley and manufacturing plants in Georgia and California.

The “Spirit of Innovation” Award is presented to an organization whose innovation in cancer measurably improves business and/or clinical processes that impact product development, prevention programs, research, or patient care.



A Link between Hormones and DNA Repair Provide New Clues to Treat Advanced Prostate Cancer

Karen Knudsen, Ph.D.

For advanced prostate cancers, new strategies for therapeutic intervention are urgently needed, and require a better understanding of how tumor cells go from slow growth to aggressive behaviors that threaten patient lives.

A new study, published by Thomas Jefferson University’s Kimmel Cancer Center researchers in the September 11th online edition of the journal Cancer Discovery, showed that hormones promote DNA repair, and that this process is critical for prostate tumor cell survival. The research also revealed a new therapeutic target that has potential for improving management for patients with advanced disease.

“We’ve known for decades that in prostate cancer, disease development and progression are dependent on the action of androgens (testosterone), but the means by which androgens promote these events remain poorly defined,” says lead author Karen Knudsen Ph.D., Professor of Cancer Biology at Thomas Jefferson University and the Deputy Director for Basic Science at Jefferson’s Kimmel Cancer Center. “The concept that androgens assist cancer cells in repairing DNA damage helps to explain how tumors evade therapeutic intervention. The good news is that these discoveries may point toward a new way to treat patients with aggressive disease.”

Inhibiting androgens is the first line of treatment for advanced prostate cancers, but this therapeutic strategy is only transiently effective, generally because tumors develop “rescue” pathways to restore androgen action. To try and understand the implications of this process, and to find means for treating such advanced disease, the researchers identified new molecular pathways involved in relaying messages from the androgen receptor to DNA repair genes. They found that androgens enhanced DNA repair by turning on the gene for a powerful DNA repair enzyme called DNAPK.

When the researchers inhibited DNAPK, they saw a reduction in tumor cell growth, and using disease models, observed that standard therapies were more effective. By acting on a more selective target in the androgen pathway, the researchers hope to improve androgen inhibition strategies and to help patients who no longer respond to androgen-inhibition-based therapies.

“These findings give us new insight into how tumors can evade existing therapies. Most importantly, the fact that prostate cancer cells use androgens and DNAPK to survive therapeutic intervention unveiled an Achilles heel for advanced tumors that we can capitalize on,” said Dr. Knudsen.

The researchers discovered that pharmacologic agents, some of which are already in clinical trials for other malignancies, can be used to suppress DNAPK activity. “The next step for us is to translate these findings into the clinical setting. Luckily, our prostate group is highly collaborative, and we are already in the midst of designing clinical trials to fast-track DNAPK inhibitors into the clinic”, said Dr. Knudsen. “There are always challenges in introducing new therapeutic targets, but if we are correct, there is every reason to believe that DNAPK inhibitors can be used to improve outcomes for patients with advanced disease.”

The study from Dr. Knudsen’s laboratory was a result of an inter-institutional team effort, including contributions of the first author and graduate student Jonathan F. Goodwin, key collaborators from the Thomas Jefferson University Department of Radiation Oncology, Dr. Adam P. Dicker, and Dr. Robert B. Den, and from the University of Michigan, Dr. Felix Y. Feng.

The authors declare that they have no conflicts of interest.

Media Only Contact:
Edyta Zielinska
Thomas Jefferson University Hospital
Phone: (215) 955-6300
Published: 9/11/2013



KCC Researchers Awarded $480,000 from Breast Cancer Research Foundation

Richard Pestell, MD, PhD and Andrew Quong, PhD

The Breast Cancer Research Foundation recently announced that Dr. Richard Pestell and Dr. Andrew Quong received unanimous approval for studies in breast cancer, the second most prevalent cancer-related cause of death in women in the United States.

Beginning October 1, 2013, Dr. Pestell will receive $240,000 to continue the “Molecular Genetic determinants of Breast Cancer Stem Cells” study and Dr. Quong will receive $240,000 to continue the “Clinical Proteomics for Breast Cancer Diagnostics” study.

Dr. Pestell’s study will focus on basal breast cancer including triple negative breast cancer, defined by the absence of three receptors (estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 [HER2]). Triple negative breast cancer is prominent among African-American women, and currently no targeted therapies for this type of breast cancer exist. Within human breast cancer a subset of cells have characteristics of stem cells (BTIC), which may contribute to recurrence and therapeutic resistance. The mechanism by which the gene DACH1 inhibits BTIC is being determined as a new approach to enhance therapeutic responsiveness. Dr. Pestell’s findings over the last year that DACH1 binds to and enhances function of the p53 tumor suppressor, but fails to bind mutations of p53 identified in human breast cancer, adds further weight to the original hypothesis that DACH1 is a breast tumor suppressor. Dr. Pestell’s studies in 2012-2013 will continue to define the role of endogenous DACH1 as a breast cancer suppressor.

Support from BCRF has also allowed Dr. Quong to complete his studies examining changes in protein levels in breast tumors. From these observed changes, Dr. Quong’s team found changes in the metabolism of tumor cells that are related to the local microenvironment of the tumor. These changes in metabolism can potentially be exploited for both imaging and drug development. In addition, Dr. Quong has continued his work identifying markers that are indicators of toxicity and response to therapy.

In 2012-2013, the goal of Dr. Quong’s research is to determine new strategies for patient treatment that include radiation therapy. By measuring the protein and gene expression in tumors, his will use this information for choosing treatment and also monitoring the patients’ response to treatment both for effectiveness and adverse side effects.



Researchers Find New Clues to Treat Rare and Aggressive Inflammatory Breast Cancer

Massimo Cristofanilli, M.D.

A study led by investigators from Thomas Jefferson University’s Kimmel Cancer Center has discovered molecular clues that may help physicians therapeutically target inflammatory breast cancer (IBC), a highly aggressive form of breast cancer.

Their study, reported in the June 21 online issue of Breast Cancer Research and Treatment, identified two molecules (ALK and FAK1) involved in the IBC cancer pathway. Drugs already exist that inhibit both of these two cancer-promoting proteins at the same time, which the researchers are now testing in animal preclinical studies.

“Women diagnosed with inflammatory breast cancer are in great need of therapies that are tailored to this aggressive form of breast cancer. Survival rates are much lower than for other forms of breast cancer,” says the study’s lead author Sandra V. Fernandez, Ph.D., Assistant Professor in the Medical Oncology department at Jefferson.

IBC is a particularly aggressive and highly metastatic form of breast cancer characterized by very rapid onset of progression— weeks to a few months — and metastasis that spreads quickly to the brain, bones, and soft tissues. The three-year survival rate is 40 percent for IBC patients compared with 85 percent in other forms of breast cancer. Additionally, IBC patients are younger when diagnosed.

The disease is also difficult to diagnose because it appears as redness and swelling of the breast. There are no classic tumor masses.

“Because of how this cancer looks, physicians often think it is dermatitis, or inflammation, or an infection, such as mastitis. I know of many patients who were misdiagnosed from the start, and by the time they were referred to an oncologist, their cancer had progressed,” says the study’s senior investigator, Massimo Cristofanilli, MD, FACP, Professor of Medical Oncology and Director of the Jefferson Breast Care Center.

“We need to improve both diagnosis and treatment of this cancer, which is on the rise for reasons that are not understood,” he says.

The advances reported in the study were possible because the research team developed a new animal model of IBC, derived from tumor  cells from a patient with metastatic triple negative (estrogen receptor-negative, progesterone receptor-negative, Her2-negative) inflammatory breast cancer under an IRB-approved study. At the present, there are few animal models to study this particular disease.

In addition to identifying some of the pathways involved in IBC, the researchers were able to characterize the pattern of spread of the disease, which moved quickly to organs and the brain. They found that clumps of the cancer — not tumor masses — obstruct lymphatic channels in the breast, causing the swelling of breast tissues.

“This animal model is a really important tool to use to study IBC progression and metastasis, and to test potentially beneficial drugs,” says Dr. Fernandez.

Researchers from the University of Texas M D Anderson Cancer Center and Fox Chase Cancer Center contributed to the research.

The study was supported by the American Airlines-Komen for the Cure Foundation Promise Grant KGO81287, NIH NCI 1R01 CA 138239, and the Inflammatory Breast Cancer Foundation.

The authors declare that they have no conflicts of interest.

For more information, contact Jackie Kozloski, 215-955-5296, jackie.kozloski@jefferson.edu.



Researchers Discover Molecule That Drives Aggressive Breast Cancer

Richard G. Pestell, M.D., Ph.D.

Recent studies by researchers at Thomas Jefferson University’s Kimmel Cancer Center have shown a gene known to coordinate initial development of the eye (EYA1) is a powerful breast tumor promoter in mice. The gene EYA1 was also shown to be overexpressed in a genetic breast cancer subtype called luminal B.

The scientists found that excess activity of this gene —EYA1 — also enhances development of breast cancer stem cells that promote resistance to cancer therapy, recurrence, and poor survival.

Because EYA1 is an enzyme, the scientists are now working to identify a natural compound that could shut down EYA1 activity, says Richard Pestell, M.D., Ph.D., Director of Kimmel Cancer Center.

“It was known that EYA1 is over-expressed in some breast cancers, but no one knew what that meant,” he says. “Our studies have shown the enzyme drives luminal B breast tumor growth in animals and the enzyme activity is required for tumor growth.”

In a mouse model of aggressive breast cancer, the research team targeted a single amino acid on the EYA1 phosphatase activity. They found that inactivating the phosphatase activity of EYA1 stopped aggressive human tumors from growing.

“We are excited about the potential of drug treatment, because it is much easier to develop a drug that targets a phosphatase enzyme like EYA1, than it is to target a gene directly,” he says.

Tracing how EYA1 leads to poor outcomes

The study, which was published in the May 1 issue of Cancer Research, examined 2,154 breast cancer samples for the presence of EYA1. The researchers then linked those findings to patient outcomes. They found a direct relationship between increased level of EYA1 and cyclin D1 to poor survival.

They then chose one form of breast cancer —luminal B — and traced the bimolecular pathway of how EYA1 with cyclin D1 increases cancer aggressiveness. Luminal B breast cancer, one of five different breast cancer subtypes, is a hormone receptor-positive form that accounts for about 20 percent of human breast cancer. It is more aggressive than luminal A tumors, a hormone receptor-positive cancer that is the most common form of breast cancer.

Their work delineated a string of genes and proteins that are affected by EYA1, and they also discovered that EYA1 pushes an increase in formation of mammospheres, which are a measure of breast cancer stem cells.

“Within every breast cancer are breast cancer stem cells, which give rise to anti-cancer therapy resistance, recurrence and metastases,” Dr. Pestell says. “We demonstrated in laboratory experiments that EYA1 expression increase the number of mammospheres and other markers of breast cancer stem cells.”

“As the EYA1 phosphatase activity drove breast cancer stem cell expansion, this activity may contribute to worse survival,” he says.

This study was supported in part by the NIH grants RO1CA132115, R01CA70896, R01CA75503, R01CA86072 and P30CA56036 (RGP), a grant from the Breast Cancer Research Foundation (RGP), a grant for Dr. Ralph and Marian C. Falk Medical Research Trust (RGP), Margaret Q. Landenberger Research Foundation, the Department of Defense Concept Award W81XWH-11-1-0303.

Study co-authors are, from Kimmel Cancer Center: first author Kongming Wu, Zhaoming Li, Shaoxin Cai, Lifeng Tian, Ke Chen, Jing Wang and Adam Ertel; Junbo Hu, from Huazhong University of Science and Technology, China; and Ye Sun, and Xue Li from Boston Children’s Hospital.

For more information: Jackie Kozloski, 215-955-5296, jackie.kozloski@jefferson.edu.



KCC Ranked as One of Best Cancer Hospitals in US

Men’s Health magazine recently ranked the Kimmel Cancer Center at Jefferson among the best in the nation, calling out its success in treating prostate cancer, a leading cancer in men.

The American Cancer Society estimates there will be more than 1.5 million new cancer diagnoses in 2013.

Jefferson scientist, Matthew Schiewer, Ph.D., recently received the Prostate Cancer Benjamin Franklin Young Investigator Award, and will use the funds to help find treatments for advanced-stage prostate cancers.

Jefferson is home to top-of-the-line equipment and high-tech features like electron and photon-beam treatment and complete 3-D treatment planning.  We offer comprehensive diagnostic and treatment options for prostate cancer in addition to state-of-the-art prostate imaging and biopsy service.

When indicated, a prostatectomy can be performed either laparoscopically or via open surgery.  Jefferson physicians were the first in the Delaware Valley to remove the prostate laparoscopically, and have extensive experience with and numerous scientific publications on the use of the da Vinci® Surgical System.

“It is rewarding for our team to be recognized for excellence in cancer care,” says Richard G. Pestell, MD, PhD, MBBS, FRACP, MBA, Kimmel Cancer Center Director.  “We are one of only eight NCI-Designated cancer centers in the United States with a prostate program formally reviewed and endorsed by the National Cancer Institute. This program, led by Leonard Gomella, MD and Karen Knudsen, PhD, is a powerhouse of key advances in prostate cancer.  Our leading edge research and clinical care excellence across a wide spectrum of cancer specialties, including men’s health, enable us to deliver the best outcomes for our patients.”

Kimmel Cancer Center at Jefferson

The Kimmel Cancer Center at Jefferson is a National Cancer Institute (NCI)-designated clinical cancer center for excellence in cancer care and research. U.S.News & World Report also recognizes Jefferson as one of the best hospitals in the nation for Cancer care. Taking into account your varied needs, our nationally renowned cancer experts bring together a team of specialists in a wide range of disciplines to work with you and your primary care or referring physician to devise a personalized treatment plan.

The physicians and scientists of the Kimmel Cancer Center have helped pioneer new approaches to cancer treatment by transforming scientific discoveries into improved patient care. Our physicians are experienced in using the most advanced treatment methods and technologies and are at the forefront of developing new therapies. As a result, you may have the opportunity to take part in one of the more than 120 clinical trials for promising new cancer treatments being conducted at Jefferson at any given time.

by Danielle Servetnick on Tuesday, July 16th, 2013 in Cancer CareIn The News.



Ladies of Port Richmond Featured in Inquirer

Mary Louise Leuters is a two-time breast cancer survivor and president of the Ladies of Port Richmond, a local group of breast cancer survivors who have raised over $400,000 for breast cancer research in the last nine years.Nearly 300,000 American women will be diagnosed with breast cancer this year, and 40,000 will die from it, according to the American Cancer Society. There are nearly three million survivors.The Ladies of Port Richmond host a local walk each year along with many fundraising events including bake sales and church breakfasts.In an interview with the Philadelphia Inquirer, Richard Pestell, MD, director of the Kimmel Cancer Center at Jefferson, explains that the money is especially valuable because it comes with no strings attached. Jefferson researchers have used it as seed money – almost impossible to find otherwise – to do preliminary research that has helped win National Cancer Institute grants worth millions. He adds, ”There’s been a tremendous return on their efforts.”

Read the full “The fighting ladies of Port Richmond” story.

Learn more about the Jefferson Breast Care Center and treatment of breast cancer at Jefferson.

by Danielle Servetnick on Wednesday, July 17th, 2013 in Cancer CareIn The News.



Keatley Foundation Donation

The Keatley Foundation made a generous $10,000 donation to the Kimmel Cancer Center.   Events like their second annual Beef and Beer contributed to this generous donation. The Keatley Foundation was created by Bob Lyons during his treatment at Jefferson Hospital. The foundation name comes from the street name where Bob lives. According to Bob, That street sign was “The sign that I started my road to recovery on every morning, gaining strength to take a few more steps towards that street sign on the corner each day”. For more about Bob’s story please see the following Jefferson Hospital blog post.

Mr. Bob Lyons presents donation check to Dr. Richard Pestell

Ms. Angela Cantone and Mr. Bob Lyons present donation check to Dr. Richard Pestell






KCC Investigator wins Prostate Cancer Foundation Benjamin Franklin Young Investigator Award

Matthew Schiewer, PhD

Matthew Schiewer, PhD

Matthew Schiewer, PhD, a postdoctoral fellow in Dr. Karen Knudsen’s lab in the Department of Cancer Biology, is the recent recipient of a Prostate Cancer Foundation Young Investigator Award. Dr. Schiewer’s investigations will focus on the role of PARP-1 in DNA damage repair and the inhibition of PARP with specific medications as a potential therapy for advanced, metastatic prostate cancer. PARP-1 may reduce cancer progression by reducing the activity of the androgen receptor, the engine of prostate cancer. This project is highly translational in nature, and a greater understanding of the relationship between PARP inhibition and AR activity may provide new therapeutic opportunities for prostate cancer patients with advanced disease.

Prostate Cancer Foundation Young Investigator awards are designed to promote long-term careers in the field of prostate cancer research by providing three-year grants for transformational research focused on prostate cancer advances and new treatments to improve patient outcomes. Since 2007, PCF has invested more than $25 million in Young Investigator awards.

Project Title: Determining the translation capacity of the PARP-1/AR axis in prostate cancer

For more info about the 2013 Awards please see the Prostate Cancer Foundation announcement.




Jefferson Post-Doc Receives National Cancer Center Fellowship

Dr. Edward Hartsough

Dr. Edward Hartsough

Edward Hartsough, Ph.D. received a post-doctoral fellowship from the National Cancer Center Organization ( http://www.nationalcancercenter.org/ ).  The fellowship grant is entitled “Next-Generation RAF Inhibitors in V600E BRAF Melanoma.”  Dr. Hartsough works in Dr. Andrew Aplin’s lab at the Kimmel Cancer Center.

The National Cancer Center was founded by Dr. J. Ernest Ayre in 1953 as a non-profit organization committed to research and education about cancer. Melanoma is the deadliest form of skin cancer and its incidence is on the rise. BRAF mutations are found in half of melanomas and the funded work will study new mutant BRAF targeting agents in preclinical models.




Massimo Cristofanilli, M.D., Appointed Director of the Jefferson Breast Care Center

Massimo Cristofanilli, M.D.

Massimo Cristofanilli, M.D., FACP, an internationally renowned breast cancer researcher and clinician, has been appointed Director of the Jefferson Breast Care Center at the Kimmel Cancer Center (KCC) and Thomas Jefferson University and Hospitals.

With more than 25 years of clinical, basic science and educational experience, Dr. Cristofanilli will also serve as Deputy Director of Translational Research at the KCC.

Prior to joining Jefferson, Dr. Cristofanilli served as chairman of the department of medical oncology at Fox Chase Cancer Center and head of the center’s Inflammatory Breast Cancer Clinic. Before that, he founded and served as Executive Director of the Morgan Welch Inflammatory Breast Cancer Program and Clinic at The University of Texas M.D. Anderson Cancer Center in Houston.

Dr. Cristofanilli is a widely-recognized leader in the translational research and treatment of inflammatory breast cancer (IBC), the rare and aggressive form of breast cancer in which cancer cells block lymph vessels in the skin of the breast. Moreover, he has recognized expertise in the development of novel diagnostic and prognostic markers in primary and metastatic breast cancer (MBC).

“Dr. Cristofanilli is a proven leader whose translational research expertise will fit in perfectly with the overall mission of the KCC to link our already excellent basic science in breast cancer with more patient-directed therapies in a time-efficient manner,” said Richard G. Pestell, M.D., Ph.D., Director of the KCC and Chair of the Department of Cancer Biology and Vice President for Oncology Services at Jefferson. “We look forward to tackling some of the most innovative questions in breast cancer precision oncomedicine with cutting edge research and the latest clinical trials.”

Dr. Cristofanilli’s research aims to improve personalized medicine for breast cancer patients, focusing on molecular targeted agents, biomarkers and gene therapies, and bridging the gap between the bench and bedside in a more practical and smarter way. A forte of Dr. Cristofanilli is his team-based and multidisciplinary approach to medicine.

His 2004 study published in The New England Journal of Medicine on circulating tumor cells (CTCs)—found to be a predictor of progression-free survival and overall survival in MBC patients—sparked a slew of subsequent preclinical and clinical investigations that continue to further our knowledge and molecular understanding of the metastatic process with the potential to impact the treatment and improve the prognosis of these patients affected by recurrent disease.

Recently, he presented a study at the 2012 San Antonio Breast Cancer Symposium on commercially-available genomic tests and their ability to better classify tumor subtypes in breast cancer to help guide treatment plans.

“We’re proud that Jefferson is the new home for Dr. Cristofanilli, whose work in cancer research and in the clinic goes unmatched and whose passion to initiate and grow programs speaks for itself, particularly for aggressive forms of breast cancer,” said Neal Flomenberg, M.D., Chair of the Department of Medical Oncology at Jefferson. “We’re looking forward to this new chapter at the Jefferson Breast Care Center and the KCC, where his experience in compassionate clinical care and cutting edge research will better serve the institution and ultimately the patients in the region and beyond.”

Dr. Cristofanilli received his medical degree from the University of La Sapienza in Rome, Italy, where he also completed a fellowship in medical oncology.  He completed an internship at the Cabrini Medical Center in New York, as well as his residency in internal medicine. That was followed by a fellowship in medical oncology at The University of Texas M.D. Anderson Cancer Center.

Dr. Cristofanilli is Board Certified by the American Board of Medical Oncology and the European Society for Medical Oncology.

“Jefferson, as an institution, has a tradition, but at the same time is always projecting towards the future, forever expanding upon research and clinical programs, bringing innovative technologies into the lab and clinic, and attracting new physicians and patients,” said Dr. Cristofanilli. “I want to bring my vision to Jefferson and look forward to us to being able to grow together.”

The Jefferson Breast Care Center was founded in 2006 and is one of 466 centers in the nation accredited by the National Accreditation Program for Breast Centers. The Center gives the patient a comprehensive experience where surgery, medical oncology, radiation oncology, radiology, pathology risk assessment / genetics, social work and a breast care navigator are all working together with the patient at the center of care.



Jefferson Opens Calorie Restriction Trial for Early Stage Breast Cancer Patients on Radiation Therapy

Nicole Simone, M.D.

Jefferson’s Kimmel Cancer Center will begin a first-of-its-kind clinical trial that uses calorie restriction to help treat early stage breast cancer patients undergoing radiation therapy.

Evidence suggests that reducing patients’ calorie intake could help shrink tumors and improve survival because it enhances the effectiveness of radiation therapy, the team explains in a recent review published in the Oncologist.

“In our research, we’ve seen a 30 percent reduction in tumor size in mice, and they live much longer than mice not on a diet,” said Nicole Simone, M.D., Principal Investigator and Assistant Professor of Radiation Oncology at Thomas Jefferson University and Hospitals. “The next step is to investigate if early stage breast cancer patients are able to adhere to caloric restriction while on radiation. This will then allow us to determine others benefits and factors, such as toxicity, recurrence, and survival.”

Until now, the use of calorie restriction to treat cancer or augment standard cancer treatment, such as radiation therapy, has received little attention, with few trials underway in the U.S. Jefferson’s trial, however, is the first in breast cancer patients.

The study is being partly funded by a donation from the Ladies of Port Richmond, a local breast cancer group that raises awareness and funds for research.

Caloric restriction has been shown to alter molecular pathways that make cancer cells more susceptible to radiation, enhancing its effectiveness and thus shrinking tumors and improving survival in mice. What’s more, clinical evidence over the last several decades has shown a link between cancer incidence and calorie restriction.

Beginning in February, Jefferson will begin enrolling 40 women on a calorie reduction diet (a 25 percent reduction of the patients typical total intake) while undergoing treatment. Stage 0 and I breast cancer patients who are not diabetic but who are candidates for breast conserving therapy will be given dietary counseling and guidance to carry out a liquid diet 36 hours prior to lumpectomy and then a calorie reduction of 25 percent will be done during radiation therapy.

Calorie restriction will start the week of radiation planning and continue for the six weeks of radiation, for a total of 10 weeks. Patients will keep a nutritional journal, have counseling in Jefferson’s own Myrna Brind Center of Integrative Medicine to tailor the diet reduction for each individual patient and also meet with counselors during weekly visits.

For the trial, the feasibility of treating breast cancer patients with a calorie-restriction diet modification in conjunction with standard radiation will be assessed. Acute toxicity as per National Cancer Institute Common Toxicity Criteria, quality of life, local recurrence, progression-free survival, distant metastases and overall survival will be also assessed.

In the lab, calorie restriction has been used prior to implantation of tumor cells in mouse breast cancer models and has been shown to slow or even prevent tumor growth.

Dr. Simone’s laboratory has investigated calorie restriction as a treatment modality, implanting tumors in mice prior to initiation of the diet to mimic the use of a diet in a newly diagnosed patient. For the second approach, calorie restriction was administered with cytotoxic therapy to determine the value of calorie restriction as part of a combination therapy.

Preliminary data demonstrated that calorie restriction repressed tumor growth when administered concurrently with radiation in two types of breast cancer: triple negative breast cancer, which has a propensity for metastases and locally aggressive breast cancer.

Calorie restriction alters molecular pathways, including the insulin and AMP-kinase pathway, the researchers posit, leaving cancer cells more sensitive to radiation therapy. Both pathways have been shown to play a role in breast cancer cell proliferation and progression of disease.

Dr. Simone presented the work at the 2012 American Society for Radiation Oncology, and has published several studies on the topic in Cell Cycle and International Journal of Breast Cancer

“Dieting is likely an effective method to enhance the cytotoxicity of radiation therapy because of the overlapping induction of molecular profiles, and it may also provide a beneficial means of improving the overall health and metabolic profiles of patients,” said Dr. Simone. “This trial could provide evidence to implement calorie restriction into the care of cancer patients in treatment. What’s more, it may provide a cost-effective addition to current treatment modalities that enhances cancer therapy while minimizing side effects.”



Jefferson Radiation Oncology Resident Looks to Improve Prostate Cancer Outcomes in Ghana

Kosj Yamoah, M.D., Ph.D.

A new study published in January in the journal BMC Cancer, led by Kosj Yamoah, M.D., Ph.D., a resident in the Department of Radiation Oncology at Thomas Jefferson University and Hospital, takes aim at the issue by investigating prostate cancer diagnoses and treatment delivery in black men living in the West African region, in order to devise research strategies to help improve health outcomes.

Overall, many men are diagnosed at a later stage, with more than half opting out of treatment, they found. The researchers point to stigmas about cancer as a root of the problem.

“Cancer could eclipse infectious diseases as an epidemic if more awareness and intervention doesn’t come about,” said Dr. Yamoah, who grew up in Ghana until age 20, when he came to the United States. “Cancer can be very hush-hush because of cultural and financial issues and social stigmas associated with the disease. We need to bring awareness and address the needs of the population and barriers to care.”

“Cancer is still perceived as a death sentence,” he added. “People are scared to go to their doctor to find out if they have it, let alone to follow through with treatment.”

In a retrospective analysis of 379 patients referred for treatment at the National Center for Radiotherapy and Nuclear Medicine at the Korle Bu Teaching Hospital (KBTH) from 2003 to 2009, the team found that 33 percent were diagnosed with metastatic disease and 70 percent had a prostate-specific antigen (PSA) score four times higher than men in the United States or Europe at time of diagnosis.

PSA screening rates in Ghana are low, the authors explain, and many men opt out of radiation therapy and other therapies after diagnosis. Out of the 251 patients eligible for radiation therapy, only 141 patients actually received external beam radiation therapy.

Among patients with at least two years of follow up after external beam radiation therapy, three- and five-year PSA-failure free survival was 73.8 percent and 65.1 percent respectively. In the U.S., those percentages are 90 percent and 85 percent, respectively.

Reasons recognized by KBTH clinicians for patients declining radiation therapy included: the prohibitive cost of treatment, fear of radiation, and a state of denial based on their perception of disease originating solely from spiritual causes rather than biologic processes.

The data, which to date provides the largest source of published information on outcomes for prostate cancer treatment in the West African region, is a call to action, according to the authors.

The research team plans to develop treatment regimens tailored to the needs of Ghanaian men, which may differ from guidelines currently utilized in the Unites States and Europe in order to better address the disease burden and improve mortality rates in Ghana. That could mean more frequent PSA screening.

“There is controversy in the United States with PSA testing, but in a country like Ghana, there may be a role for PSA screening, even infrequent screening, because of all the late stage cancers we are finding,” said Dr. Yamoah.

The team has established collaboration between two institutions with the hope of improving prostate cancer treatment and plan to start more clinical trials to develop novel, shorter course treatments for locally-advanced prostate cancer.

“Based on these results, our group has proposed a plan for future research aimed at identifying an appropriate role for PSA screening in this population, developing radiation therapy treatment schedules that better fulfill the needs of Ghanaian prostate cancer patients, and contributing to understanding genetic factors associated with prostate cancer risk and treatment response,” the authors write.

Sarah E. Hegarty, a statistical analyst in the Department Pharmacology & Experimental Therapeutics at Jefferson, and Terry Hyslop, Ph.D., also of the Department Pharmacology & Experimental Therapeutics at Jefferson, were also part of the study.



Phone and Mailed Interventions Significantly Increase Colorectal Cancer Screening Rates

Ronald Myers, Professor of Medical Oncology

A mailing or phone call to help patients get screened for colorectal cancer significantly increases their chances of actually getting tested, according to a study published in the January issue of Cancer Epidemiology, Biomarkers and Prevention by researchers at the Kimmel Cancer Center at Jefferson.

The research team, led by Ronald E. Myers, Ph.D., Professor and Director of Division of Population Science, Department of Medical Oncology at Thomas Jefferson University, performed a randomized, controlled trial of 945 people aged 50-79 to test the impact of a new, preference-based navigation intervention, as opposed to standard mailing or usual care, on screening rates.

A third of the patients received a “tailored” phone call to encourage them to perform their preferred screening test (colonoscopy vs. at-home blood stool test), plus a mailing of preferred information; another third were sent information on colonoscopy and a stool blood test kit; while the last third received no intervention.

Patients who received a phone call and/or mailing were almost three times as likely to undergo screening six months later compared to those who had no intervention. However, there was no significant difference between the phone and mailed interventions versus mailings only on screening rates.

While colorectal cancer screening rates are increasing in the United States, rates lag behind those for breast and cervical cancer screening. Screening and early detection of colon and rectal cancer holds tremendous promise for reducing the toll of colon and rectal cancer.

Colorectal cancer is the third leading cause of cancer death in this country with more than 140,000 new cases diagnosed each year. Late diagnoses will account for many of the colorectal cancer related deaths.

The study, which was conducted between 2007 and 2011, included 10 primary care practices affiliated with the Christiana Care Health System in Delaware that used a comment medical record system.

The research team searched for patients who had no prior diagnosis of colorectal neoplasia or inflammatory bowel diseases, had visited one of the participating practices within the previous two years, and were not compliant with American Cancer Society colorectal cancer screening guidelines.

For the study, 312 patients received a tailored intervention, where they were informed about both colonoscopy and blood stool tests and then were sent information on colonoscopy or the actual blood test performed, based on their preference. Another group, consisting of 316 patients, was mailed information about both colonoscopy and stool blood test performed.  The remaining 317 were sent no information or tests and did not receive any phone calls.

Overall screening adherence at six months was significantly higher in both invention groups compared to the control group, the researchers found. Thirty-eight percent of patients who received the tailored phone interventions and 33 percent of patients who received mailings completed screening tests. Only 12% of patients in the control group completed screening tests.

In terms of the intervention groups, the researchers found that preference-based navigation did not significantly boost overall adherence to a level that was significantly higher than that achieved by mail, but increased participant performance of their preferred screening test in comparison to the mailed intervention, especially colonoscopy use.

“The study showed that both strategies were superior to usual care, and that there is not a one-size fits all approach to screening,” said Dr. Myers. “The next step is to determine if an intervention strategy that maximizes screening test access, incorporates patient preference, and engages providers can achieve higher screening rates compared to just mailings.”



Radiation Oncology Services Expanding at Riddle Hospital

Jefferson Radiation Oncology at Riddle Memorial Hospital is pleased to announce that the expansion of Radiation Oncology services has begun.

In the next few months, the Department will begin installing a new True –Beam linear accelerator, Brachytherapy High Dose Rate machine and a CT scanner.

Construction is expected to be completed by December 2013.

The acquisition of this new technology at Riddle Hospital will allow Jefferson physicians to offer the latest cancer treatment techniques, while utilizing state-of-the-art equipment.

Riddle Hospital offers a wide variety of cancer services including support groups, free cancer screenings, diagnostic techniques, treatments and educational programs, to name a few.

For more information, visit http://www.kimmelcancercenter.org/jkccn/members/riddle-memorial-hospital.html



Bench to Bedside: How to Fast Track Targeted Cancer Drugs with Radiation into the Clinic

Researchers from the translational research program of the National Cancer Institute and the Radiation Therapy Oncology Therapy Group have developed new guidelines to help fast track the clinical development of targeted cancer drugs in combination with radiation therapy.

The suggested strategic guidelines, published in the Journal of the National Cancer Institute in a recent commentary with lead author Yaacov Richard Lawrence, MRCP, an adjunct Assistant Professor in the Department of Radiation Oncology at Thomas Jefferson University and Director of the Center for Translational Research in Radiation Oncology at Sheba Medical Center in Israel, offers specific steps in the preclinical and early phase clinical trial process to get well-studied and novel targeted agents into the clinic more quickly.

Over the last decade, molecular agents that target cellular survival and growth, like Erlotinib and Sunitinib, have been developed but alone have had modest effect on improved survival. Combining such targeted agents with radiation therapy, however, has the potential to improve cure rates and long-term overall survival.

“There’s a missed opportunity in today’s cancer care treatment,” says Dr. Lawrence. “There is very promising laboratory data out there, but the clinical development of these new drugs with radiation has been limited. Here, we have put together a road map to help overcome obstacles and speed the development of new pipeline drugs with radiation.”

Adding radiation therapy to existing chemotherapy agents to radiation therapy has improved survival, and the authors of the commentary, which includes Adam P. Dicker, Chair of the Department of Radiation Oncology at Jefferson, believe new targeted therapies can follow in the same path.

“We know we want to repeat that success with new biological drugs,” says Dr. Lawrence. “In order to do that, we need direction, which is sorely lacking. These guidelines explicitly explain how much evidence is needed to go forward from the lab into the clinic, and furthermore how to design the clinical trials in humans.”

The guidelines discuss key questions when investigating specific targeted agents and tumor types, designing new clinical trials, such as the ‘time-to-event continual reassessment method design’ for phase I trials, and randomized phase II “screening” trials, and the use of surrogate endpoints, such as pathological response.

It also discusses the role and purpose of preclinical studies in radiation oncology drug development and how to identify new, radiation response agents.

There are challenges to drug development with radiation, the authors explain. A major problem is the limited interest from the pharmaceutical industry in developing drugs with radiation, which is of special importance since the pharmaceutical industry fund a large amount of clinical cancer research. Furthermore, significant individual skills and institutional commitments are also required to ensure a successful program. The situation has been extenuated by the decrease in radiation biologists in recent years.

It is hoped that by providing a clear pathway, the guidelines will help the field overcome these barriers and create a focus and interest in drug development.
Some new approaches, the researchers say, include combining radiosensitizers with hypofractionated (high daily dose) radiation schedules and integrating immunomodulators with radiation therapy.

“We feel passionate that a a good way to push clinical care forward for cancer patients is by combining these two types of treatment: advanced radiation treatment together with the new generation of anticancer drugs,” says Dr. Lawrence. “We know where the future lies, and guidelines provide the path to bring us there.”

The full guidelines in the JNCI can be found here: http://jnci.oxfordjournals.org/content/early/2012/12/07/jnci.djs472.full



More Designated Time Equals More Published Research for Radiation Oncology Residents

What helps radiation oncologist residents publish more academic research?

Giving them more time to do it, physicians in the Department of Radiation Oncology at Thomas Jefferson University Hospital conclude in a study published recently in the Journal of American College of Radiology.

Based on results from a web-based survey completed by 97 radiation oncologists and current senior residents from academic medical centers across the country, the biggest factor contributing to more first-author publications for residents is the amount of designated research time given during residency.

Anecdotally, there seems to be much variability in the productivity of radiation oncology residents. Some publish numerous articles, whereas others produce less. However, what leads to this variability remains undefined.

It appears that previous individual accomplishments or values among residents—often thought of as critical factors—seem to play less of a role than time and structure of a program.

To determine the predictors, researchers from Jefferson and Drexel University College of Medicine, invited 232 radiation oncologists and senior residents to partake in the web-based survey.

The survey addressed demographic factors, previous academic accomplishments, and residency program structure. The end point—research productivity—was defined as the number of first-author papers produced or research grants awarded on the basis of work initiated during residency.

There was a 42 percent response rate, most of whom were women. The median number of publications produced on the basis of work during residency was three. The average amount of dedicated research time was six months. 16 percent had less than three months. The more time a resident had, the more papers they published.

The results imply that academic success is not simply the result of innate ability but rather the structural aspects of residency programs.

“Medical research by residents is an important part of training, contributes to the academic growth of the radiation oncology field, and ideally makes them better physicians,” said Robert B. Den, M.D., Assistant Professor of Radiation Oncology at Jefferson and author of the paper.  “The structure of a program highly influences resident research capability,” he added.

Other authors on the paper includes Jordan M. Gutovich of Drexel University, Maria Werner-Wasik, M.D., Associate Professor of Radiation Oncology at Jefferson, Adam P. Dicker, M.D., Ph.D., Chair of Radiation Oncology at Jefferson, and Yaacov Richard Lawrence, MRCP, an adjunct Assistant Professor in the Department of Radiation Oncology at Jefferson University and director of the Center for Translational Research in Radiation Oncology at Sheba Medical Center in Israel.

The full study can be found here: http://www.jacr.org/article/S1546-1440%2812%2900386-9/abstract



Game changing diagnostic & prognostic prostate cancer genetic tests revealed by KCC researchers

Richard Pestell, M.D., Ph.D.

Researchers at the Kimmel Cancer Center at Jefferson (KCC) have developed potentially game-changing diagnostic and prognostic genetic tests shown to better predict prostate cancer survival outcomes and distinguish clinically-relevant cancers.

The team, led by Richard G. Pestell, M.D., Ph.D., Director of the KCC and the Chair of the Department of Cancer Biology at Thomas Jefferson University, report their preclinical findings from a blinded, retrospective analysis of over 350 patients and mouse study in a recent issue of the journal of Cancer Research.

Using an oncogene-specific prostate cancer molecular signature, the researchers were able to separate out men who died of prostate cancer versus those who lived, and more specifically, identifying men who died on average after 30 months (recurrence free survival). The diagnostic test distinguished patients with clinically relevant prostate cancer from normal prostate in men with elevated prostate-specific antigen (PSA) levels.

The researchers worked with three oncogenes previously associated with poorer outcomes in prostate cancer: c-Myc , Ha-Ras, and v-Src.

The test, the researchers say, is superior to several previously published gene tests and to the Gleason scale, which is a rating given to prostate cancer based upon its microscopic appearance and currently used to help evaluate the prognosis of men with the disease.

Given the diversity of prostate cancer outcomes—some men live two years after diagnosis, others live for more than 20 more years— a new oncogene-specific signature like this could not only help better identify prostate cancer risk but also test targeted therapies—by way of a new prostate cancer cell line.

These studies describe the first isogenic prostate cancer cell lines that metastasize reliably in immune competent mice. Previous studies were in immune deficient mice.

“This oncogene signature shows further value over current biomarkers of prediction and outcomes,” said Dr. Pestell. “Such a signature and cell line may also enable the identification of targets for therapies to better treat prostate cancer, which takes the lives of over 27,000 men a year.”

In breast cancer, the identification of tumor subsets with various gene signatures has improved clinical care for patients because of targeted therapies.

The work here by the KCC aims to identify gene patterns and subsequent tests in prostate cancer that could serve similar purposes. But to help develop such therapies, model systems that closely resemble human disease are required. To date, there have been several limitations with currently available cell lines.

Although important transplantation experiments have been conducted using human prostate cancer cell lines in immune deficient animals, the immune system plays an important role in prostate cancer onset and progression making it imperative to develop prostate cancer cell lines that can be studied in immune competent animals.

Also, although the transgenic mouse has been an effective model to study the molecular basis of human cancers, the prostate cancer mouse models have long latency and often unpredictable metastasis.

Here, the researchers succeeded in overcoming these issues.

The oncogene-specific prostate cancer molecular signatures were recapitulated in human prostate cancer and validated in distinct populations of patients as a prognostic and diagnostic test.

What’s more, the researchers demonstrated how the isogenic prostate cancer cell lines metastasized in immune-competent mice.

“Identification of gene signatures in breast cancer has allowed for a deeper understanding of the disease, and this paper moves us steps closer to being able to follow a similar trajectory with prostate cancer. Today, such an understanding and a formidable testing ground for new therapies is lacking for this disease,” Dr. Pestell said. “With this new oncogene-specific prostate cancer molecular signature, we have a valuable prognostic and diagnostic resource that could help change the way we manage and treat prostate cancer.”

###

Other researchers in the study include Xiaoming Ju, Adam Ertel, Mathew Casimiro, Zuoren Yu, Hui Meng, Peter A. McCue, Rhonda Walters, and Paolo Fortina.