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.

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.

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.”

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.

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.”

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

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

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

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.

Karen Knudsen, Ph.D.

Elevated levels of Cyclin D1b could function as a novel biomarker of lethal metastatic disease in prostate cancer patients, according to a pre-clinical study published ahead of print on December 21 in the Journal of Clinical Investigation by researchers at the Kimmel Cancer Center at Jefferson.

The group, headed by Karen E. Knudsen, Ph.D., Professor and Hilary Koprowski Chair, Departments of Cancer Biology, Urology, and Radiation Oncology at Thomas Jefferson University and Deputy Director for Basic Science at the KCC, found that Cyclin D1b, a variant of the cell cycle regulator Cyclin D1a, functions independently of the cell cycle to promote metastasis in both early and late stage prostate cancer.

Rather, Cyclin D1b, but not Cyclin D1a, regulates a large gene network, the researchers found, which was shown to cooperate with androgen receptor (AR) signaling to fuel metastatic progression in multiple models of prostate cancer.

Studies have shown that Cyclin D1b expression is elevated in early stages of prostate cancer (in up to 30% of primary disease), and researchers have now demonstrated that this occurs more frequently in late stage castration-resistant prostate cancer: up to 80%.

Cyclin D1b expression is also highly correlated with that of the pro-metastatic gene SNAI2 (Slug), which the group identified as regulated by cooperative signaling between Cyclin D1b and AR.

“Numerous clinical and pre-clinical studies have effectively demonstrated that AR signaling is critical for progression to metastatic disease, but our knowledge of AR targets which can induce metastatic phenotypes is limited,” said Dr. Knudsen. “Our data describe how cross talk between the cell cycle and AR can rewire the AR signaling axis to enhance the expression of genes which elicit metastasis in both early and castration resistant prostate cancer models.”

“We found that Cyclin D1b can directly promote AR dependent expression of the gene SNAI2 (Slug), which dramatically increased metastatic events to soft tissues in animal models,” she added.

Metastatic castration resistant prostate cancer represents the most lethal form of the disease, which arises when AR is reactivated despite continued hormone therapy.

Soft tissue metastasis to the liver and lung represents a particularly aggressive form of prostate cancer, whose presence predicts for decreased survival time in prostate cancer patients.

Currently, there is little knowledge as to how these metastatic events occur, and identification of pathways and biomarkers of this lethal event could greatly benefit prostate cancer patients.

Using various in vitro and in vivo models, researchers found that Slug enhances the ability of cells to colonize soft tissues, which resulted in a higher incidence of metastasis in the liver and lung.

Given the inability to manage AR signaling in metastatic castration resistant prostate cancer, Slug driven pathways could be leveraged to dramatically limit the incidence of soft tissue metastasis and improve patient morbidity and mortality, researchers believe.

“Identification of AR driven pathways which mediate metastatic progression represents a significant leap forward in our attempts to effectively manage prostate cancer progression,” said Dr. Knudsen. “Cyclin D1b and Slug can likely be used as biomarkers to identify patients with an increased risk of metastasis, and will eventually provide us with novel “druggable” targets downstream of AR and Slug which can be exploited to dramatically reduce the incidence of these lethal metastatic tumors.”

This study was completed as a result of an inter-institutional team effort, including the contributions of the lead author and graduate student Michael A. Augello of the Department of Cancer Biology at Thomas Jefferson University, as well as key collaborators: Dr. Felix Feng (University of Michigan), Dr. Alessandro Fatatis (Drexel University), Dr. Tapio Visakorpi (University of Tampere), Dr. Donald McDonnell (Duke University), Dr. C. Burd (University of Ohio), Dr. D E. Frigo (University of Houston) and Dr. Ruth Birbe of Thomas Jefferson University.

Renato V. Iozzo, M.D., Ph.D.

Renato Iozzo, M.D., Ph.D.,  a Professor of Pathology, Anatomy and Cell Biology at Thomas Jefferson University, has recently been appointed as Editor-in-Chief of the journal Matrix Biology beginning January 2013.

This flagship journal is published by Elsevier and is affiliated with both the International Society for Matrix Biology and the American Society for Matrix Biology. Dr. Iozzo served as president of both societies between 2007 and 2010.  Dr. Iozzo’s  efforts follow those of Dr. Bjorn Olsen from Harvard Medical School.

Dr. Iozzo is als  a long-standing member of the graduate program in Cellular and Developmental Biology.  He is also Professor of Biochemistry and Molecular Biology and a member of Jefferson’s Kimmel Cancer Center since its foundation.

His research interest is focused on the biology of proteoglycans and their roles in cancer and angiogenesis. He has published over 280 peer-reviewed articles, numerous reviews and edited two books on proteoglycans. His work is one of the most cited in the Proteoglycan and Matrix Biology fields, with over 18,000 citations and an h-index of 76

Scott Waldman, M.D., Ph.D., chairman of the Department of Pharmacology and Experimental Therapeutics

Scott Waldman, M.D., Ph.D., chairman of the Department of Pharmacology and Experimental Therapeutics at Thomas Jefferson University, has been awarded one of the prestigious “Provocative Questions”  grants from the National Cancer Institute (NCI) , as part of the Institute’s ambitious program to tackle the “important but not obvious” questions in cancer to ensure no stone was left unturned  after decades of promising research.

Scientists have known for a long time that obesity contributes to cancer risk, but they don’t know why.

That’s one of the questions set forth by the NCI—24 in total—that Dr. Waldman will help answer with a four-year grant for almost $1.2 million. Out of 700 applicants, just 57 recipients from institutions nationwide were chosen.

For Dr. Waldman, the answers behind cancer and obesity may lie in a hormone receptor known as guanylyl cyclase C (GCC), found mostly in the intestinal tract.

GCC has been established as a suppressor of colorectal cancer tumors and a useful tool to better predict colon cancer risk and recurrence by Dr. Waldman and his team. Preclinical and clinical studies found that lower levels of GCC were associated with an increased risk for colorectal cancer. They also discovered administering GCC reversed that trend.

More recent studies have revealed GCC’s role in appetite. The researchers found that silencing GCC affected appetite in mice, disrupting satiation and inducing obesity. Conversely, mice who expressed the hormone receptor knew when to call it quits at mealtime.

Now, under the “Provocative Questions” program, Dr. Waldman will further explore the relationship between cancer and the hormones regulating GCC to get a deeper understanding of the mechanisms of the risk posed by obesity—and a possible therapeutic target to treat it.

This is a promising notion, given that one-third of the U.S. population is considered obese, and that obese people have a 50 percent increased risk of being diagnosed with colorectal cancer.

“We are proposing that obesity increases colorectal cancer risk by suppressing the expression of those hormones, and silencing GCC,” said Dr. Waldman, “which is an effect that can be reversed by dietary calorie restriction or oral GCC hormone replacement therapy.”

There is potential for immediate translation of results to help reduce colorectal cancer risk in obese patients, given that an oral GCC drug to treat constipation just received regulatory approval, added Dr. Waldman, who is a member of Jefferson’s Kimmel Cancer Center.

The Provocative Questions project emerged from discussion among a number of veteran cancer researchers that noticed there were many questions — some important but not very obvious, some that had been asked but abandoned in the past because there were no ways to study or address them, some sparked by new discoveries or novel technologies — that could stimulate the NCI’s research communities to use laboratory, clinical, and population sciences in especially effective and imaginative ways.

More than 50 grants, attempting to answer 20 of the 24 proposed questions, with $22 million are being funded this year from that set of applications.

This research is supported by the National Cancer Institute of the National Institutes of Health under award number R01CA170533-01.

Marja Nevalainen, M.D., Ph.D., associate professor of Cancer Biology, Medical Oncology and Urology at Jefferson Medical College of Thomas Jefferson University and Jefferson’s Kimmel Cancer Center

Men who had high levels of the activated Stat5 protein in their prostate cancer after a radical prostatectomy were more likely to have a recurrence or die from the disease compared to men who had little to no presence of the growth protein, according to a recent study published in Human Pathology by Jefferson’s Kimmel Cancer Center researchers.

This suggests, Stat5, a protein that when activated signals cancer cells to grow and survive, could be an ideal biomarker to help guide patients and physicians for future treatment.

The research team, led by Marja Nevalainen, M.D., Ph.D., associate professor of Cancer Biology, Medical Oncology and Urology at Jefferson Medical College of Thomas Jefferson University and Jefferson’s Kimmel Cancer Center, examined prostate cancer biopsies and tumor tissues obtained from 562 men who underwent a radical prostatectomy, comparing Stat5 levels with outcome.

They also looked at prostate tumor tissue in 106 patients who were under a “watchful waiting” or active surveillance treatment plan and had no neoadjuvant therapy. Samples were taken at the time of diagnosis.

“In both cohorts, if the patient had increased Stat5 in their prostate cancer, that patient was more likely to experience prostate recurrence or die from his disease compared to patients who had very low levels of Stat5,” said Dr. Nevalainen.

More specifically, patients without detectable nuclear Stat5a/b expression had recurrence-free survival of 72 percent at eight years. In contrast, patients with high nuclear Stat5a/b score had a recurrence-free survival rate of 42 percent at eight years. This indicates an approximately 30 percent benefit in recurrence-free survival at eight years associated with negative status for nuclear Stat5a/b expression in prostate cancer.

For those on active surveillance, patients with low nuclear Stat5a/b scores had a lower probability of prostate cancer specific death. There was an approximate 50 percent benefit in prostate cancer specific survival at 10 years associated with a negative status for Stat5.

The findings support a series of past and ongoing studies investigating Stat5 and its predictive capabilities led by Dr. Nevalainen.

A study from 2005, published in the journal Clinical Cancer Research, showed similar findings to this current study. Activated Stat5 in prostate cancer predicted outcome; however, there were differences in the cohorts. The key limitation of the previous study was the heterogeneous cohort of the patients, who received different adjuvant therapies at the time / after radical prostatectomy.  In the present study, the patients received a single mode of surgical intervention with no neoadjuvant therapies.

In 2008, in a another study published in Clinical Cancer Research, researchers showed that they can effectively kill prostate cancer cells in both the laboratory and in experimental animal models by blocking Stat5. That provided a proof of principle that Stat5 is a therapeutic target protein for prostate cancer.

Next, the group will be investigating Stat5’s predictive response after radiation therapy.

“There is an urgent need for reliable biomarkers to identify prostate cancer patients whose cancer is most likely to recur after the initial therapy and progress to advanced disease,” said Dr. Nevalainen. “The data presented here supports the initiation of prospective studies to determine the clinical utility of Stat5 as a prognostic and predictive marker in prostate cancer.”

Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award number R01CA113580.

Several media outlets covered the study, including Urology Times and Prostate Cancer Foundation news section. Links to those article are below.

“Protein predicts post-RP cancer recurrence, death”

“Stat5 Predicts Early Disease Recurrence and Prostate Cancer Specific Deaths in Patients After Radical Prostatectomy”

The release was picked up by  Science Daily, Medical News Today, and Yahoo! News.

A newly discovered function of PARP-1 could be the key to more effective therapeutics to treat advanced prostate cancer patients, a recent preclinical study published in Cancer Discovery by Jefferson’s Kimmel Cancer Center researchers suggests.

Karen E. Knudsen, Ph.D., Professor in the Departments of Cancer Biology, Urology, & Radiation Oncology

The team, led by Karen E. Knudsen, Ph.D., Professor in the Departments of Cancer Biology, Urology, & Radiation Oncology at Thomas Jefferson University, found that functions of PARP-1 not only include DNA damage repair but also androgen receptor (AR) regulation in advanced prostate cancer growth and progression.  PARP inhibition in various models was found to suppress AR activity, which fuels prostate growth.

Researchers believe that the dual functions of PARP-1—as both a regulator of AR as well as critical for DNA damage repair—could be leveraged for therapeutic benefit.  PARP inhibitors could slow down advanced-stage prostate cancer and shrink tumors, the team surmises.

“We hope to capitalize on this previously unknown function in PARP-1 in prostate cancer,” said Dr. Knudsen. “Our data show that PARP-1 plays a major role in controlling AR function and that, when suppressed with inhibitors, enhanced anti-tumor effects of castration and delayed onset to castration resistance. “

“This is the basis to support a clinical trial investigating PARP-1 inhibitors in patients with advanced disease,” she added.

Today, PARP-1 is seen as a valuable target because of its involvement in DNA damage repair for cancer cells. The therapy has been successful when combined with DNA-damaging drugs because it heightens the apoptotic activity of these drugs. In other words, it helps halt tumor growth by stopping DNA repair in various cancers.

Prostate cancer is dependent on AR activity for growth and survival, and is largely resistant to standard chemotherapy. AR-directed therapies are the first-line intervention for patients with advanced disease; however, recurrent tumors arise when AR is reactivated, a common occurrence in the castrate-resistant stage of the disease.

Therefore, there is a dire need to develop means to suppress the AR function in these patients. With this new role defined, PARP inhibitors targeting both functions could sensitize prostate cancer cells to DNA damage, and potentially improve the efficacy of AR-directed therapies in these patients, the researchers suggest in the paper.

Almost 40 percent of men with prostate cancer progress into an advanced stage, termed castrate-resistant prostate cancer, where chemotherapy and other therapies have little to no effect.

Using various in vitro and in vivo model systems, the researchers found that PARP-1 activity is required for AR function and is increased in castrate-resistant prostate cancer.  Additionally, inhibiting PARP-1 suppressed proliferation of cultured, primary human tumor specimens in a state-of-the-art system.

“These findings introduce a paradigm shift with regard to PARP-1 in prostate cancer,” said Dr. Knudsen, “and provide the basis for new therapies that could help a whole population of cancer patients who have little options.”

Dr. Knudsen recently received a two-year Challenge Award worth $1 million from the Prostate Cancer Foundation (PCF) for her work with PARP-1 and prostate cancer, and attended PCF’s 10^th annual fundraiser in Philadelphia.

The study from Dr. Knudsen’s laboratory was a result of an inter-institutional team effort, including the contributions of lead author and postdoctoral fellow Dr. Matthew Schiewer, of the Department of Cancer Biology at Thomas Jefferson University, as well as key collaborators: Dr. Felix Feng (University of Michigan), Drs. Wayne Tilley and Lisa Butler (University of Adelaide), Dr. Ganesh Raj (UT Southwestern), Dr. Peter McCue, Dr. Leonard Gomella, Dr. Adam Dicker, Dr. Jonathan Brody, and Dr. John Pascal of Thomas Jefferson University.

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This work was supported by NIH grants (R01 CA099996-09, and R01 ES016675-11), the Commonwealth of Pennsylvania grant, a Prostate Cancer Foundation Creativity award, a Prostate Cancer Foundation Young Investigator Award grants from the National Health and Medical Research Council of Australia, a Cancer Council of South Australia Senior Research Fellowship, and Pre-doctoral Fellowships from the DOD.

Renato V. Iozzo, M.D., Professor of Pathology, Anatomy and Cell Biology, at Thomas Jefferson University

A natural substance found in the surrounding tissue of a tumor may be a promising weapon to stop triple negative breast cancer from metastasizing.

A preclinical study published in PLOS ONE September 19 by Thomas Jefferson University researchers found that decorin, a well-studied protein known to help halt tumor growth, induces a series of tumor suppressor genes in the surrounding tissue of triple negative breast cancer tumors that help stop metastasis.

“These findings provide a new paradigm for decorin, with great implications for curbing tumor growth by inducing new tumor suppressor genes within the tumor microenvironment, and for the discovery of novel gene signatures that could eventually help clinical assessment and prognosis,” said senior author Renato V. Iozzo, M.D., Professor of Pathology, Anatomy and Cell Biology, at Thomas Jefferson University.

Triple negative breast cancer is the most deadly of breast cancers, with fast-growing tumors, that disproportionately affect younger and African-American women. Today, no such marker is applied in care of triple negative breast cancer, and as a result, patients are all treated the same.

“Originally, we thought that decorin was affecting the tumor, but, surprisingly, decorin affects the so-called tumor microenvironment, where malignant cells grow and invade, igniting genes to stop such growth,” said Dr. Iozzo, who is also a member of Jefferson’s Kimmel Cancer Center. “Absence of decorin in the microenvironment could explain metastasis in some patients, where higher levels of the protein may keep cancer from spreading.”

In the study, 357 genes were found to be induced by the increased presence of decorin, but more interestingly, the researchers discovered that three of these genes, which were previously unlinked to triple negative breast cancer, were tumor suppressor genes affecting the tumor microenvironment, including Bmp2K, Zc3hav1, and PEG3.

Decorin is a naturally occurring substance in the connective tissue where, among other roles, it helps regulate cell growth by interacting with growth factors and collagen. A decade ago, Dr. Iozzo and his team discovered that decorin, a cell protein, and specifically, a proteoglycan, is increased in the matrix surrounding tumor cells. They also discovered that decorin causes production of a protein, p21, which also can arrest cell growth. However, decorin’s role in breast cancer and the mechanism behind its anti-tumor properties remained elusive.

For this study, researchers aimed to investigate the impact of decorin in triple negative breast cancer tumors using human cell lines in mice, as well analyze gene expression activity in the tumor microenvironment.

Tumors treated with decorin were found to have a decreased volume of up to 50 percent after 23 days. Using a sophisticated microarray technique, the researchers then analyzed the mouse tumor microenvironment, finding increased expression of 357 genes, three of which are the tumor suppressor genes of interest.

These results demonstrate a novel role for decorin in reduction or prevention of tumor metastases that could eventually lead to improved therapeutics for metastatic breast cancer.

“Here, we have a molecule that can turn a tumor microenvironment from a bad neighborhood to a clean neighborhood by inducing genes in that neighborhood to stop growth and prevent the tumor from metastasizing,” said Dr. Iozzo.

Eagles player Jason Avant and Dr. Leonard Gomella, Chair of Urology at Jefferson

September is Prostate Cancer Awareness month, and Thomas Jefferson University Hospitals has again teamed up with the Philadelphia Eagles to educate fans and others about prostate health and to raise cancer awareness.

To help kick off the campaign, Jefferson will serve as the presenting partner at the Sunday, September 16 game versus the Baltimore Ravens, with Edouard Trabulsi, M.D., Director of Multidisciplinary Genitourinary Oncology Center of the Kimmel Cancer Center at Jefferson (KCC),  and David P. McQuaid, FACHE, President, Thomas Jefferson University Hospitals, Inc., receiving Eagles jerseys on the field before kickoff.

“The KCC and our Departments of Urology, Medical Oncology and Radiation Oncology are deeply honored and grateful to once again have the Eagles as our partners,” said Leonard Gomella, MD, chair of the Department of Urology at Thomas Jefferson University Hospitals and director of clinical affairs at the KCC. “Prostate cancer is the second leading cause of cancer death among men, and over 200,000 will be diagnosed this year alone.  That’s why it’s so important for men to take their prostate health seriously.”

Prostate cancer is the most common type of cancer among men, with one in six men being diagnosed in his lifetime, and most treatable if caught early.

“In the months ahead, Jefferson and the Eagles look forward to more victories on the field and in raising prostate cancer awareness,” Dr. Gomella said.

Eagles wide receiver Jason Avant is also joining forces with Jefferson to help spread prostate health awareness, participating in several community events and a public service announcement with Dr. Gomella on the importance of prostate health and screening.

For the 23^rd consecutive year, Jefferson Hospitals will also offer free prostate health and cancer screenings on September 19 and 25 from 9 a.m. to 3 p.m. (registration required). Call 1-800-JEFF-NOW to make an appointment.

In August, The Eastern Cooperative Oncology Group (ECOG) voted to approve Jefferson’s Kimmel Cancer Center and Thomas Jefferson University Hospital as a Provisional Member.

ECOG is one of the largest clinical cancer research organizations in the United States, and conducts clinical trials in all types of adult cancers. It constitutes a large network of private and public medical institutions that work toward developing various protocols for effective cancer treatments.

It was established in 1955 as one of the first cooperative groups launched to perform multi-center cancer clinical trials.

Funded primarily by the National Cancer Institute (NCI), ECOG has evolved from a five member consortium of institutions on the East Coast to one of the largest clinical cancer research organizations in the U.S. with almost 6000 physicians, nurses, pharmacists, statisticians, and clinical research associates (CRAs) from the U.S., Canada, and South Africa.

Institutional members include universities, medical centers, Community Clinical Oncology Programs (CCOPs), and Cooperative Group Outreach Programs (CGOPs). These institutions work toward the common goal of controlling, effectively treating, and ultimately curing cancer. Research results are provided to the worldwide medical community through scientific publications and professional meetings.

Currently, ECOG has more than 90 active clinical trials in all types of adult malignancies. Annual accrual is 6,000 patients, with more than 20,000 patients in follow-up.

For more information, please visit http://www.ecog.org/

Karen Knudsen, Ph.D.

A group of investigators led by Dr. Karen Knudsen was awarded a 2-year challenge grant of one million dollars by the Prostate Cancer Foundation.  The details of this award (from the PCF web site) are:

2012 Movember-PCF Challenge Award

Lead Investigator:
Karen Knudsen, PhD
Thomas Jefferson University

Title
Interrogation of Aberrant DNA Repair in Sporadic Prostate Cancer

Co-investigators: Johann De Bono, MD, PhD, Royal Marsden Hospital; Felix Feng, MD, University of Michigan; Mark Rubin, MD, Weill Cornell Medical College.

What this means to patients: Understanding the extent and impact of alterations in DNA Damage Response pathways in prostate cancer patients will target specific DNA repair problems and allow effective Precision Medicine (tailored treatment regimens) based on molecular subtyping of patient DDR alterations matched to drug therapy.

Synopsis: DNA Damage Response (DDR) pathway alterations are changes in DNA repair mechanisms that promote genomic instability and have been associated with local and advanced prostate cancer. Dr. Knudsen and team will identify and comprehensively determine the frequency of abiraterone in DDR pathways at different stages of prostate cancer progression. They will determine the clinical relevance of these DNA repair defects in prostate cancer patients and their role in the development and progression of treatment-resistant prostate cancer. Previous studies showed that the DNA repair protein PARP1 is elevated in tumors of advanced prostate cancer patients. PARP1 is recruited to sites of androgen receptor function and is required for AR activity in both hormone-dependent and treatment refractory disease. PARP inhibition therefore has dual effects on cancerous cells; 1) impairs DNA repair in tumors and, 2) suppresses AR signaling—halting cancer progression. Dr. Knudsen and colleagues will evaluate effects of combination therapy with PARP inhibitors and next generation anti-androgens in treatment-resistant prostate cancer patients.

Congratulations to Dr. Onder Alpdogan and Dr. Jianqing Lin for each being selected recipients of an ACS-IRG award.

The American Cancer Society-Institutional Research Grants (ACS-IRG) are designed to provide seed money to support junior faculty members with an interest in cancer research. The ACS defines junior faculty as investigators at the rank of assistant professor or equivalent who are eligible to apply as a principal investigator for grant support from national agencies.

Jianqing Lin, M.D., assistant professor of medical oncology

Dr. Lin’s Research Overview
The current proposal is a continuation of the concept that digoxin is an inhibitor of HIF-1a that will subsequently slow the growth of prostate cancer progression. Since the drug has minimal toxicity, it would be an ideal therapy to explore in other disease states in prostate cancer. With the awareness of over-treatment and treatment related complications in men with low-risk localized prostate cancer patients are willing to be on active surveillance. This current proposal is to examine the effects of digoxin to delay or reverse prostate cancer progression, with significant effort on tissue acquisition and to understand the molecular pathway affected with the treatment of digoxin. This study will shed light on the effects of future HIF-1a inhibitors for the treatment of prostate cancer and the foundation for future NIH funding.

Dr. Alpdogan’s Research Overview

Onder Alpdogan, M.D., assistant professor of medical oncology

Use of haploidentical HSCT in the treatment of advanced/relapsed RCC is a novel idea and has never been studied in preclinical models. We believe that haploidentical transplant model is a better platform to develop immunotherapy to solid tumors specificall renal cell carcinoma. Immunological response would be faster than other transplant models because of MHC disparity. This innovative new approach might give us an opportunity to develop new treatment strategies for patients with resistant/relapsed RCC after exhausting standard therapy including cytokine (IL-2) and Tyrosine Kinase Inhibitors (TKIs). These studies will not only generate new information about clinically relevant treatment strategies, but also provide substantial new findings about stem cell biology and transplantation.

Voichita Bar-Ad, M.D., an associate professor in the Department of Radiation Oncology at Thomas Jefferson University Hospital

Voichita Bar-Ad, M.D., an associate professor in the Department of Radiation Oncology at Thomas Jefferson University Hospital and Jefferson’s Kimmel Cancer Center, has been named Residency Program Director.

Dr. Bar-Ad is a board-certified radiation oncologist who treats primarily head and neck and gastrointestinal cancer cases. Her research focuses on treatment-related side effects and toxicities, patient quality of life and symptom management. She has paid specific attention to radiation-induced oral mucositis for head and neck cancer patients treated with radiotherapy or concurrent chemoradiotherapy, using the intensity- modulated radiation therapy technique.

“I am devoted to my patients and immersed in my research projects, but teaching is my joy, my passion,” Dr. Bar-Ad said last fall when she was named an “Educator of the Year” by the Association of Residents in Radiation Oncology (ARRO).

“This new role as Program Director enables me to continue what I love to do, guiding and teaching residents,” said Dr. Bar-Ad. “I’m greatly honored, and feel fortunate to lead a program that trains the radiation oncologists of tomorrow to have excellent clinical and research skills.”

Radiation oncology residency at Jefferson is a four-year training program, with resident having already completed one year of post-graduate training in medicine, surgery, or a transitional program.

The residency in radiation oncology trains residents broadly in cancer management and emphasizes interdisciplinary care.  Faculty members provide instruction in all modes of radiation oncology:  megavoltage photon- and electron-beam therapy, interstitial and intracavitary radioactive-source implantations, stereotactic radiosurgery and radiotherapy, intensity modulated radiation therapy and the diagnostic and therapeutic uses of radioactive isotopes.

In addition to the residents unanimously selecting Dr. Bar Ad for the ARRO 2011 Teacher of the Year Award, they also selected her to receive the 2012 Department of Radiation Oncology’s “Teacher of the Year Award,” an honor bestowed every June by the residents to the one faculty member who has helped them the most in their educational experience.

Jefferson’s Residency Program became accredited in 1973, but has been in existence since 1960.  The first resident, Dr. Carl Mansfield, went on to become a Chair of the Department, a position he maintained until May 1995, when he went to the National Cancer Institute to serve as a director of the Radiation Research Program

“Thomas Jefferson University Hospital has created one of the nation’s most outstanding residency programs in radiation oncology, and it is with great honor to have such a distinguished physician, researcher and teacher help continue that tradition,” said Adam P. Dicker, M.D., Ph.D., Chair of the Department of Radiation Oncology. “A strong residency program is essential for the successes of an academic medical center, and I look forward to having Dr. Bar-Ad’s leadership bring significant benefits to our residents and patients.”