Need to Analyze Your Next-Generation Sequencing Data? Thomas Jefferson University’s New Web-Based Resource Makes the Task Easy

Isidore Rigoutsos, Ph.D.

In the early 1990s, an international effort was launched by the U.S. Department of Energy and the National Institutes of Health to sequence the human genome. The project took 13 years, involved many scientists in several countries, and cost $2.7 billion (in FY 1991) dollars.

Since then, technological advances and the advent of next generation sequencing have greatly increased the speed at which the genome or the transcriptome of a model organism such as human or mouse can be sequenced. Nowadays, a typical sequencing platform can generateseveral billion bases of DNA or RNA in the course of a few days and can do so at a far lower cost.

However, such an embarrassment of riches poses difficulties for the typical research groups who would like to make use of this technology but are neither accustomed nor equipped to handle the great amounts of data that can now be generated. To help address this problem, Thomas Jefferson University is making available to researchers and clinicians such an analytical capability on the web.

The resource, referred to as HandsFree, is a system that was designed and implemented by the Computational Medicine Center at Thomas Jefferson University. The goal of HandsFree is to provide researchers and clinicians at Thomas Jefferson University and Hospitals with the ability to analyze the large datasets that next generation sequencing platforms generate. And since HandsFree is web-based, scientists at other universities, in the Delaware Valley and elsewhere, could also take advantage of it.

“It is a unique resource to academic research and medicine,” says Isidore Rigoutsos, Ph.D., Director of the Center. “I don’t know of any other research institution or medical center that currently makes a similar system available to their researchers and clinicians.”

How does it work? Dr. Rigoutsos offers as an example a researcher who wants to understand a particular aspect of the biology of Alzheimer’s disease, and who has brain samples taken from a deceased patient, as well as samples from a normal brain. The investigator would give the samples to the sequencing facility at the Kimmel Cancer Center at Jefferson and several days later she will get back data files typically containing 200 million sequences for each sequenced sample, he says.

“This is where HandsFree comes in,” Dr. Rigoutsos says. “The investigator can access HandsFree through her computer browser, securely transfer the sequencing dataset to the HandsFree web-server, and answer a few questions about the type of data and desired analyses. At this point, the data will be placed in a queue with other datasets for analysis by the Computational Medicine Center’s computers. When the dataset reaches the front of the queue, it will be quality-trimmed and preprocessed, then mapped on the corresponding genome followed by a series of analyses that are typical for such data.”

“The system will also generate genomic maps for the investigator to also enable subsequent off-line visual exploration. The generated results and maps are then placed back on the HandsFree web-server and the investigator is notified through email that the output is ready for collection,” he says.

“The whole process is as hands-free as it can get for these kinds of datasets,” Dr. Rigoutsos says. “The investigator still has some work ahead of them but the system does all the ‘heavy lifting’ for them taking the guess-work out and making this kind of analysis easy to harness.”

It took his team one and a half years to put the HandsFree system together. The underlying pipeline uses both publicly available standard tools as well as tools that the team specifically developed to automate the whole process. “HandsFree enables others to access the very same pipeline that we use ourselves for our own basic research. In this regard, the pipeline’s components have already been ‘vetted’ by us,” says Dr. Rigoutsos.

Very importantly, the system handles the data in a secure fashion, he adds. “Any data that the investigator exchanges with HandsFree is encrypted in both directions. Moreover, the processing and analyses of the data are carried out by the Center’s machines in a separate and secure high performance computing facility.”

Currently, the HandsFree system can accommodate DNA and RNA datasets generated by several popular sequencing platforms, from both human and mouse. “For these datasets, the user can carry out a number of standard analyses at the click of a button,” Dr. Rigoutsos says. “A whole host of additional capabilities is in the process of being implemented and will be enabled in HandsFree in the months ahead.”

The system is now available to researchers, and the cost for analyzing these datasets “is very reasonable,” he says. “HandsFree will help advance medical science, and we are very pleased to have it online and available to our researchers and to others.”

The system can be accessed at http://cm.jefferson.edu/HandsFree

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



Tool to Ensure Accuracy of Radiation Treatment Plan Will Improve Quality and Save Time for Cancer Patients

It is critical that a cancer treatment plan that uses radiation be checked, and checked again, before patients are exposed to the therapy. Radiation mistakes can reduce survival, increased toxicity, and result in poor tumor control. Evaluating the radiation treatment plan, however, can be time-consuming and labor-intensive, especially in large-scale multi-institutional clinical trials, say radiation physicists at Thomas Jefferson University and at China’s Fudan University.

Now, these physicists have collaboratively developed a computer-based plan-quality evaluation program they say improves quality and efficiency for cancer patients participating in clinical trials.

In the May 14 issue of Physics in Medicine and Biology, investigators demonstrates that use of a semi-automated process improves review efficiency by reducing human error and minimizing wait times for patients.

Physicist Jiazhou Wang, M.S., from the Department of Radiation Oncology at Fudan University Shanghai Cancer Center and physicist Ying Xiao, Ph.D., of Thomas Jefferson University lead respective international collaborative team efforts to develop the quality improvement methodology, which can also be used in a clinical setting.

“The tools developed from the study will benefit Chinese radiation oncology departments where a large number of patients are being cared for,” says Zhen Zhang, M.D., Ph.D., Chairman of Radiation Oncology at Fudan University Shanghai Cancer Center.

In multi-institutional clinical oncology trials, verifying medical physics plan quality takes time, and is both laborious and costly. This study evaluated reducing the waiting period for treatment by automating critical data parameters for multiple benefits.  It measured the effectiveness of an XML (Extensible Markup Language)-based data collection system in plan-quality evaluation.

The study found that there was a slight improvement in data accuracy, but a marked improvement in evaluation time.  XML was developed to create a plan evaluation report, which improves the clarity of specific dose-volume and other indices thereby improving communication and simplifying future analysis, says Dr. Xiao.

“As comprehensive radiation treatment technologies become more precise, our ability to effectively evaluate plan quality through improved communication tools among multi-disciplinary physicians and researchers improves patient care,” states Adam Dicker, M.D., Ph.D., Professor and Chairman of radiation oncology, Thomas Jefferson University Hospital.

Fudan University Shanghai Cancer Center (FUS), one of the largest cancer centers located in Shanghai, will become the first affiliate member of the Radiation Therapy Oncology Group, sponsored by the Department of Radiation Oncology, Thomas Jefferson University, Kimmel Cancer Center. “This historical accomplishment was achieved by a decade of close collaboration between physicians and scientists from Fudan University Shanghai Cancer Center and Thomas Jefferson University,” Dr. Dicker says.

This work was funded in part by the NCI P30 grant to the Kimmel Cancer Center, Thomas Jefferson University.

For more information, contact: 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.



Dr. Iozzo’s recent PNAS publication shows link between decorin to autophagy in endothelial cells

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

Dr. Renato Iozzo, MD, PHD, Professor of Pathology & Cell Biology, Biochemistry & Molecular Biology and Kimmel Cancer Center member, and his group recently published results in the Proceedings of the National Academy of Science (PNAS) which show decorin functions as a tumor suppressor/anti-angiogenesis factor, in part, by inducing the autophagy of endothelial cells. The publication details are below:

Buraschi, S., Neill, T., Goyal, A., Poluzzi,C., Smythies,J., Owens, R.T,  Schaefer, L., Torres,A. and Iozzo, R.V., Decorin causes autophagy in endothelial cells via Peg3.  Proc. Natl. Acad. Sci. USA 110 (28): E2582-E2591, 2013 PMID:23798385

This paper was selected by the faculty of 1000 and highlighted in Science Daily and in Extracellualr Matrix News, 4.27, 2013.

For more information please see the pubmed abstract or the full text at PNAS.



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.




2013 Kimmel Cancer Center Ball

On Saturday June 8th, 2013, the Kimmel Cancer Center held its 4th Ball at the Ritz Carlton Philadelphia. Edward Glickman, the Kimmel Cancer Center’s first Advisory Board Chairman was honored and presented with the “Spirit of Commitment” Award.

Please look here for more details about the 2013 KCC Ball.

A gallery from the Ball is below:



Kimmel Cancer Center “All Hands” Meeting

The Kimmel Cancer Center held it’s quarterly “All Hands” meeting on May 1, 2013. Dr. Richard Pestell, Director of the Kimmel Cancer Center, delivered his quarterly “State of the Cancer Center” address. Awards were presented in four categories. A special “Lifetime Achievement” Award was presented to Jouni J. Uitto, MD. The Basic Science Award was presented to Scott Waldman, MD, PhD. The Clinical Science Award was presented to Nicole Simone, MD. The Administration Award was present to Oliver Dutton. Also a special presentation on the services offered by Cancer Genomics Shared Resource was present by Paolo Fortina, MD.

Dr, Jouni Uitto receives Special "Lifetime Acheivement" Award from Dr. Richard Pestell

Dr. Scott Waldmn Receives Basic Science Award From Dr. Richard Pestell

Dr. Nicole Simone Receives Clinical Science Award From Dr. Adam Dicker

Mr. Oliver Dutton Receives Administration Award From Ms. Mika Harding



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.




Team Jefferson at 2013 Get Your Rear in Gear Race

Mika Harding, Richard Pestell, and Ruslan Banatskiy at this year's GYRIG race

Supporters of the Kimmel Cancer Center joined “Team Jefferson” for this year’s Get Your Rear in Gear 5K and 10K runs, 2 mile walk or a kids’ fun run.

Proceeds support cutting edge research in colorectal cancer and compassionate care.

Maria Grasso, founder and organizer of GYRIG Philadelphia, presented a check to Jefferson from last year’s event proceeds in the amount of $50,000 a week before the race.

A resident of Mount Laurel, N.J., Grasso lost her own father and grandfather to colon cancer.   Inspired by a desire to fight the diseases that claimed her loved ones, Grasso has grown the event from a few hundred participants to more than 4,000 as she approached the fifth year.

This annual race event is part of awareness and fund-raising efforts during March, National Colorectal Cancer Awareness Month.



Jefferson Graduate Student Receives 2013 Joanna M. Nicolay Melanoma Foundation Award

JMNMF President Greg Safko and Jefferson's Curtis Kugel

Curtis Kugel, a Thomas Jefferson University graduate student in the Department of Cancer Biology, was one of 10 students from leading cancer centers across the U.S. to receive a $10,000 “Research Scholar Award” (RSA) from the Joanna M. Nicolay Melanoma Foundation (JMNMF) for his exceptional research work.

JMNMF Chair, Regina Shannon Bodnar, and Board/RSA Committee member, Esther Hoffberg.  and JMNMF President Greg Safko, presented the award to Mr. Kugel at the Kimmel Cancer Center’s Bluemle Life Sciences Building on March 20.

Kugel was also accompanied by Dr. Richard Pestell, Director of the Kimmel Cancer Center, and Andrew Aplin, Ph.D., an Associate Professor in the Department of Cancer Biology.

Kugel’s research focuses on targeting receptor tyrosine kinases in an attempt to prevent resistance to RAF inhibitors in melanoma and improve the efficacy of those inhibitors.

“I am very excited to have been chosen to receive this award from the JMNMF for my work on melanoma research,” said Kugel. “With applicants working alongside some of the leading melanoma researchers and applying from some of the country’s top cancer centers, receiving this award is truly an honor.”

The JMNMF is a nonprofit public charity founded in January 2004 to foster melanoma education, advocacy and research. In just eight years, the Foundation has grown dramatically to become an influential voice in the melanoma community and is now established as a national, and international, “voice for melanoma prevention, detection, care and cure.”

The nationally competitive grants increased by nearly 11 percent in 2013 (following a 30 percent funding increase in 2011) to significantly enhance the potential for advancements in the melanoma cancer field and encourage a larger number of students to choose melanoma research as their professional career path.

The 2013 RSA applicant pool and cancer research centers represented grew to include 44 of the country’s most promising young melanoma researchers, and 28 prominent National Cancer Institute (NCI)-Designated Cancer Centers.

As first in the U.S. to fund graduate student melanoma researchers, the JMNMF program is celebrating the program’s seventh anniversary.

According to Regina Shannon Bodnar, “Our Foundation’s ‘Research Scholar Awards’ are invaluable at the grassroots level, to specifically grow interest in melanoma research, at leading cancer research centers nationwide.  If we can attract the brightest young minds, that are considering or are already within the nation’s cancer research pipelines, to pursue a career in melanoma research – we’re that much closer to better understanding the disease, identifying the means for effective treatments and, most importantly, finding a cure for this deadly and increasingly prevalent disease.”

For more information about JMNMF, please visit: http://www.melanomaresource.org/



Remembering ASCO Founding Member Dr. Jane Cooke Wright

Standing left to right - Dr. LaSalle D. Leffall, Jr.; Dr. Robert L. Comis; Dr. Stanley R. Hamilton; Dr. Randall C. Morgan; Dr. Al B. Benson, III; Dr. Edith P. Mitchell. Seated – Dr. Jane Cooke Wright.

In February, the American Society of Clinical Oncology (ASCO) announced the passing of Jane Cooke Wright, M.D., a true pioneer, mentor, and renowned researcher. Dr. Wright was one of seven founding members of ASCO – the only woman among the founders – and the Society’s first Secretary/Treasurer. She died on Tuesday, February 19 at the age of 93.

Pictured above, Dr. Edith Mitchell, a Clinical Professor of Medicine and Medical Oncology in the Department of Medical Oncology at Jefferson Medical College of Thomas Jefferson University, and Director of the Center to Eliminate Cancer Disparities, is joined by other ASCO members and physicians, with Dr. Wright seated.



2nd Annual Spring Fling

Please join us for our 2nd Annual Spring Fling benefiting the Helping Hand Fund for cancer patients and caregivers.

Save The Date Announcement

April 12, 2013
8:00 PM to MIDNIGHT
The Waterfall Room
2015 S. Water Street, Philadelphia, PA 19148

Tickets $50.00
Includes buffet dinner, top-shelf open bar,
dancing, raffles, 50/50 and door prizes

Contact Mia Burgis or Nicole Ferroni
mia.burgis@jefferson.edu or nicole.riverso@yahoo.com



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



Karen Knudsen, Ph.D., Appointed Deputy Director of Basic Science at Thomas Jefferson University

Thomas Jefferson University and the Kimmel Cancer Center are pleased to announce that Karen E. Knudsen, Ph.D., has accepted the position as Deputy Director of Basic Science, and will hold the prestigious Hilary Koprowski Chair in the Department of Cancer Biology.

Dr. Knudsen received her Ph.D. from the University of California at San Diego in 1996, focusing on cell cycle checkpoint control.  Her postdoctoral studies with Dr. Webster K. Cavenee at the Ludwig Institute for Cancer Research cultivated a program centered on the mechanisms underlying hormone-dependent cell cycle control.

Dr. Knudsen was recruited to Thomas Jefferson University in 2007 (now a Professor in the Departments of Cancer Biology, Urology, & Radiation Oncology) after a successful career at the University of Cincinnati College of Medicine, where she was a tenured Associate Professor.  In addition to her duties as the Deputy Director, Dr. Knudsen also serves as Leader of the Kimmel Cancer Center Biology of Prostate Cancer Program, and Director of the Greater Philadelphia Prostate Cancer Working Group.

Dr. Knudsen’s research interests are dedicated to understanding the mechanisms by which hormone receptor and cell cycle deregulation lead to prostate cancer progression and therapeutic bypass.  The overall goal of Dr. Knudsen’s laboratory is to utilize this information for successful development of precision medicine, so as to improve therapeutic outcome and patient care through rational therapy delivery.  Her studies identifying tumor suppressor and hormone receptor alterations have uncovered new targets for treating advanced disease, and led to development of biomarker-driven clinical trials.

Dr. Knudsen serves on a multitude of national boards and committees, including those for the American Association for Cancer Research, the Endocrine Society, and the Prostate Cancer Foundation.  She has been a Senior Editor for Cancer Research since 2007, is an Associate Editor for Endocrine-Related Cancer, and sits on the editorial boards of Molecular Cancer Therapeutics, the American Journal of Pathology, Molecular Endocrinology, and Oncogene. Most recently, Dr. Knudsen was appointed Editor-in-Chief of Molecular Cancer Research by the American Association for Cancer Research.  Dr. Knudsen has received numerous awards for her research, including the Ronald Ross Award for Excellence in Hormone-dependent malignancies from the Pacific Rim Breast and Prostate Cancer Research Organization, and the Richard E. Weitzman Laureate Award from the Endocrine Society.