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.”



NCI Awards ‘Provocative Questions’ Grant to Thomas Jefferson University Researcher Scott Waldman

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.



ASCO: Younger Colon Cancer Patients Have Worse Prognosis at Diagnosis, Yet Better Survival

Younger patients with colorectal cancer were more likely to present advanced stage tumors at diagnosis and metastasize much sooner, yet had better than or equal survival to patients 50 and older, according to data being presented at the 2012 American Society of Clinical Oncology Annual Meeting in Chicago. (Abstract #3621, Monday, June 4, 8:00 AM – 12:00 PM CST, S Hall A2).

The study was led by Edith Mitchell, M.D., a clinical professor in the Department of Medical Oncology at Jefferson Medical College of Thomas Jefferson University. Dr. Mitchell is also Director of the newly-established Center to Eliminate Cancer Disparities at Jefferson’s Kimmel Cancer Center.

“We’re seeing more advanced tumors in this population because the cases aren’t being caught early enough,” said Dr. Mitchell. “Screening isn’t recommended until age 50, and the younger a patient is, the more likely they are to ignore symptoms of more advanced stages of the disease.”

The objective of this study was to assess pathological features and outcomes of colorectal cancer in patients less than age 50 using an institutional sample and comparing to the Surveillance, Epidemiology and End Results (SEER) database.

Dr. Mitchell and colleagues obtained data from the tumor registry of Thomas Jefferson University Hospital (TJUH) on 4,595 patients treated for colorectal cancer from 1988 to 2007. They compared those data with data obtained from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) database on 290,338 patients with colorectal cancer treated from 1988 to 2004. The researchers collected data on location, stage and histologic grade of the cancer.

Patients under age 50 with colorectal cancer presented with more advanced stage tumors in both data sets (SEER and TJUH), and had more poorly differentiated tumors than older patients, the researchers found. Patients under 50 also had more mucinous/signet ring cell tumors with 12 percent to 8.1 percent in the TJUH data and 13.2 percent to 10.3 percent in the SEER data, with younger males having the highest prevalence in both data sets.

Younger patients had fewer right-side tumors than patients 50 and over, and a higher proportion of rectal tumors. Patients under age 50 were also more likely to have positive nodes at all stages relative to 50 and over, as well as more likely to develop peritoneal metastases, but less likely to have lung metastases than older patients.

Despite their poor pathologic features, patients under age 50 had better than or equal survival to those 50 and older, which may in part be explained by their overall health. Early evidence suggests that younger patients are able to tolerate more aggressive cancer therapies because of fewer co-morbidities, said co-author Scott Goldstein, M.D., of Jefferson’s Department of Surgery.

“Ongoing studies will help clarify the survival disparity and assess differences in treatment and molecular features between younger and older colorectal cancer patients,” Dr. Mitchell said.

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Other researchers included Allan Topham, Pramila R. Anne, of Jefferson’s Department of Radiation Oncology, Gerald Isenberg, M.D., of Jefferson’s Department of Surgery, Fran Guiles of Jefferson’s Oncology Data Services, and Juan Palazzo, M.D., of Jefferson’s Department of Pathology, Anatomy and Cell Biology.

Also see: Thomas Jefferson University Hospital Oncologists and Surgeons Treating More Colon Cancer Patients Under 50



Dr. Ronald Myers selected to chair Expert Working Group discussion

Ronald E. Myers, Ph.D.

Ronald Myers, Ph.D., Professor of Medical Oncology and Director of the Division of Population Science at Thomas Jefferson University, has been selected to chair an Expert Working Group discussion at the World Endoscopy Organization meeting on May 18, 2012. The discussion entitled “Improving Population Engagement in Screening” is being held ahead of the DDW Conference in San Diego, CA. and will be the Expert Working Group’s first meeting. The focus of this discussion is Engaging Populations in International CRC Screening Programs.

For more information on this event please contact Dr. Myers at Ronald.Myers@Jefferson.edu or 215-503-4085.



Scott Waldman Awarded CURE Grant to Move Colon Cancer Test Closer to Commercialization

Scott Waldman, M.D., Ph.D.

Scott Waldman, M.D., Ph.D., Chair of the Department of Pharmacology and Experimental Therapeutics at Thomas Jefferson University, has been awarded a Commonwealth Universal Research Enhancement (CURE) grant for almost $750,000 to help advance a molecular diagnostic test for colon cancer into commercialization.

Such a test would better detect recurrence in a group of colon cancer patients whose metastases are hidden, and help reduce racial disparities, particularly in the African-American community, who are at higher risk of dying from metastatic disease.

The nonformula grant was awarded competitively from the Pennsylvania Department of Health. One of this year’s priorities for the Department’s Health Research Advisory Committee is Cancer Diagnostics or Therapeutics with Commercialization Potential.

About 25 percent of colon cancer patients who are deemed node-negative, or pN0, (meaning the cancer has not spread to the lymph nodes) after treatment end up recurring with metastatic disease.  Known as occult tumors, these hidden metastases often escape detection, be it imaging modalities or histopathology.

Today, no such test exists to distinguish these colon cancer patients, and as a result, they are often treated the same.

To better stratify this group, Dr. Waldman and colleagues have developed a diagnostic test that uses the hormone receptor guanylyl cyclase C (GCC) as a biomarker.

Previous research shows that a quantitative, molecular analysis of lymph nodes in patients deemed colorectal cancer-free was found to be an effective predictor of recurrence. Expression of GCC in the nodes, they found, is associated with an increased risk.

“This approach can improve prognostic risk stratification and chemotherapeutic allocation for these colon cancer patients,” said Dr. Waldman, a member of Jefferson’s Kimmel Cancer Center. “With this CURE grant, we can now move a much-needed technology closer to commercialization, meaning closer to patients.”

The test will ultimately determine who can benefit from adjuvant chemotherapy, which is designed to eradicate whatever occult disease is left after surgery and other treatments.

This test would benefit the African-American community, in particular. Beyond the general population risk, there is an established stage-specific difference in outcomes in pN0 African Americans, who are 40 percent more likely to die from the metastatic colon cancer than whites.

Stratifying these patients could ultimately reduce related racial disparities in mortality and survival.

The primary purpose of this nonformula grant is to support research activities that commercialize and bring to market new cancer diagnostics and therapeutics for which proof of concept has previously been demonstrated and has the capability to solve or diminish a specific problem related to the diagnosis or treatment of one or more malignant diseases.



Rawls Palmer Progress in Medicine Award Presented to Dr. Scott A. Waldman

Scott A. Waldman, M.D., Ph.D., will receive the American Society for Clinical Pharmacology and Therapeutics (ASCPT) Rawls–Palmer Progress in Medicine Award at the 2012 Annual Meeting on March 16.

Established in 1978 by Dr. W. B. Rawls, the award recognizes scientists who have implemented progressive research techniques and tools to improve patient care.

Scott Waldman, M.D., Ph.D.

ASCPT will present the award to Dr. Waldman prior to his lecture at the 113th Annual Meeting.

Dr. Waldman is the Samuel MV Hamilton Endowed Professor of Medicine, Vice President of Clinical and Translational Research, and Chair of the Department of Pharmacology and Experimental Therapeutics at Thomas Jefferson University. He is also Director of the Gastrointestinal Malignancies Program at the university’s Kimmel Cancer Center and Associate Dean of Clinical and Translational Sciences at Jefferson Medical College.

As a longtime volunteer leader of ASCPT, Dr. Waldman has participated on various committees and task forces, serving on the Board of Directors, as Society president, and as Editor in Chief of Clinical Pharmacology and Therapeutics since 2006.

Dr. Waldman has chaired numerous scientific review panels for the NIH and is on the editorial boards of Personalized Medicine, Expert Reviews in Clinical Pharmacology, and Regenerative Medicine, among others. He is the inaugural Deputy Editor of Clinical and Translational Science and the inaugural Senior Editor of Biomarkers in Medicine.

Dr. Waldman is a recognized clinician–investigator whose research ranges from molecular biology to cancer diagnostics and therapeutics. He received the 2010 ASCPT Henry Elliott Award and the 2011 Pharmaceutical Research and Manufacturers of America Foundation Award in Excellence for Clinical Pharmacology and Therapeutics.

About ASCPT

ASCPT is the leading forum for the discussion, development, and integration of clinical pharmacology in the drug development continuum—from discovery to safe and effective use. Headquartered in Alexandria, Virginia, ASCPT was established in 1900. Today, more than 2,100 ASCPT members are committed to advancing the science of human pharmacology and therapeutics worldwide.

*This release was reprinted with permission from ASCPT.



Stronger Intestinal Barrier May Prevent Cancer in the Rest of the Body, New Study Suggests

Scott Waldman, M.D., Ph.D., chair of the Department of Pharmacology and Experimental Therapeutics at Jefferson and director of the Gastrointestinal Cancer Program at Jefferson’s Kimmel Cancer Center

A leaky gut may be the root of some cancers forming in the rest of the body, a new study published online Feb. 21 in PLoS ONE by Thomas Jefferson University researchers suggests.

It appears that the hormone receptor guanylyl cyclase C (GC-C)—a previously identified tumor suppressor that exists in the intestinal tract—plays a key role in strengthening the body’s intestinal barrier, which helps separate the gut world from the rest of the body, and possibly keeps cancer at bay. Without the receptor, that barrier weakens.

A team led by Scott Waldman, M.D., Ph.D., chair of the Department of Pharmacology and Experimental Therapeutics at Jefferson and director of the Gastrointestinal Cancer Program at Jefferson’s Kimmel Cancer Center, discovered in a pre-clinical study that silencing GC-C in mice compromised the integrity of the intestinal barrier.  It allowed inflammation to occur and cancer-causing agents to seep out into the body, damaging DNA and forming cancer outside the intestine, including in the liver, lung and lymph nodes.

Conversely, stimulating GC-C in intestines in mice strengthened the intestinal barrier opposing these pathological changes.

A weakened intestinal barrier has been linked to many diseases, like inflammatory bowel disease, asthma and food allergies, but this study provides fresh evidence that GC-C plays a role in the integrity of the intestine.  Strengthening it, the team says, could potentially protect people against inflammation and cancer in the rest of the body.

“If the intestinal barrier breaks down, it becomes a portal for stuff in the outside world to leak into the inside world,” said Dr. Waldman. “When these worlds collide, it can cause many diseases, like inflammation and cancer.”

The role of GC-C outside the gut has remained largely elusive. Dr. Waldman and his team have previously shown its role as a tumor suppressor and biomarker that reveals occult metastases in lymph nodes. They’ve used to it better predict cancer risk, and have even shown a possible correlation with obesity.

Reporting in the Journal of Clinical Investigation, Dr. Waldman colleagues found that silencing GC-C affected appetite in mice, disrupting satiation and inducing obesity. Conversely, mice who expressed the hormone receptor knew when to call it quits at mealtime.

However, its role in intestinal barrier integrity, inflammation, and cancer outside the intestine is new territory in the field.

A new drug containing GC-C is now on the verge of hitting the market, but its intended prescribed purpose is to treat constipation.

This study helps lays the groundwork, Dr. Waldman said, for future pre-clinical and clinical studies investigating GC-C’s abilities beyond those treatments in humans, including prevention and treatment of inflammatory bowel disease and cancer.

“We’ve shown that when you pull away GC-C in animals, you disrupt the intestinal barrier, putting them at risk for getting inflammatory bowel disease and cancer.  And when you treat them with hormones that activate GC-C it helps strengthen the integrity of the intestinal barrier,” Dr. Waldman said.  “Now, if you want to prevent inflammation or cancer in humans, then we need to start thinking about feeding people hormones that activate GC-C to tighten up the barrier.”



Kimmel Cancer Center at Jefferson Celebrates 20 Years of Patient Care and Cancer Discovery

October 2011 marks 20 years of exceptional cancer care and research at KCC

From October forward, the Kimmel Cancer Center at Jefferson (KCC), a National Cancer Institute-designated cancer center, is celebrating 20 years of service to the community and the groundbreaking cancer research from the scientists and physicians who’ve provided an invaluable contribution to medical science and healthcare.

“This is truly a milestone for the Kimmel Cancer Center—it’s two decades of caring and collaborating to beat cancer,” says Richard Pestell, M.D., Ph.D., director of the KCC and Chair of the Department of Cancer Biology at Thomas Jefferson University.

“With our multidisciplinary approach, KCC’s team of clinicians and researchers has continued to put their best feet forward to provide excellent, stand-out personalized care for cancer patients in the Philadelphia region and beyond and uncover new pathways to better prevent, diagnose and treat the disease,” he added.

Today, the KCC offers up an experienced team of medical and radiation oncologists, surgeons, pathologists, urologists, neurosurgeons, nurses and other specialists for patients as they fight against cancer. With the Jefferson Breast Care Center, the Bodine Center for Radiation Therapy, the Myrna Brind Center of Integrative Medicine, and Jefferson Pancreatic, Biliary Tract and Related Cancer Center, to name a few, patients have access to the best facilities, providers and technologies for cancer screening and treatment.

It was October 1991 when the Jefferson Cancer Institute opened, with the dedication of the Bluemle Life Science Building on the Thomas Jefferson University campus. Four years later, with the awarding of a Cancer Center Support Grant, the National Institutes of Health National Cancer Institute (NCI) officially recognized it as one of only 54 NCI-designated cancer centers in the U.S. at the time. The institute took its current name in 1996 when businessman and philanthropist Sidney Kimmel made a generous donation to the institute to expand its research activities.

The donation to Jefferson is not a “gift,” but “an investment for humanity,” Mr. Kimmel told the Philadelphia Inquirer in 1996. “I really believe we’re going to have a breakthrough” in cancer research.

Living up to his expectations, KCC cancer researchers have made significant contributions over the last two decades, including better care in prostate cancer (Leonard Gomella, M.D.); new targets and diagnostics for prostate and breast cancer (Hallgeir Rui, M.D., Ph.D., Dr. Pestell); discoveries in colon cancer (Scott Waldman, M.D., Ph.D); pioneering discoveries in cancer metabolism and stem cells (Michael Lisanti, M.D. Ph.D., Dr. Pestell); better bone marrow transplants (Neal Flomenberg, M.D.); more selective radiation treatment (Adam Dicker, M.D.); and new areas of the human genome to treat (Isidore Rigoutsos, Ph.D., and  Paolo M. Fortina, M.D., Ph.D.).

Dr. Pestell, who became director in 2005, has made significant contributions to understanding cell cycle regulation and the aberrations that can lead to cells turning cancerous. His work identified new molecular markers, and new targets for cancer treatment. An internationally renowned expert in oncology and endocrinology, Dr. Pestell’s record of research funding is outstanding, securing substantial National Institutes of Health grants for the KCC.

Today, KCC’s well-funded basic science programs include cell biology, immunology and structural biology, developmental therapeutics, melanoma, leukemia/lymphoma, prostate and breast cancers, and gastrointestinal and genitourinary cancers. KCC also conducts numerous cancer clinical trials each year aimed at prevention and treatment of cancer.

Two recent clinical trials have resulted in the addition of new procedures at Thomas Jefferson University Hospital.  For example, in the Department of Urology, under chairman Leonard Gomella, M.D, a bladder cancer diagnostic tool using an imaging agent and blue light technology is now helping physicians better detect tumors along the bladder lining. Also, a new, two-step approach to half-match bone marrow transplants (where a patient can use a sibling or parent as a donor) developed by Chair of Medical Oncology Neal Flomenberg, M.D., is proving to be a success for blood cancer patients whose options were otherwise limited.  Jefferson is the only hospital in the region performing half-match procedures.

Since being appointed as chair of the Department of Radiation Oncology in 2010, Adam Dicker, M.D., Ph.D., has led extensive clinic renovations and the ongoing addition of new technologies. That includes Bodine’s recently acquired radiation therapy equipment for head and neck and prostate cancer patients and an upcoming radiosurgey instrument designed to deliver higher doses of radiation to smaller areas. Bodine’s state-of-the-art brachytherapy suite is also set to open in early 2012.

Last year, Charles J. Yeo, M.D., Chair of Surgery, performed his 1,000th Whipple procedure.  The Whipple procedure is a major surgical operation involving removal of portions of the pancreas, bile duct and duodenum, and is typically performed to treat malignant tumors involving the pancreas, common bile duct or duodenum.  Jefferson’s surgery department treats more pancreatic cases than anywhere in the region.

Thomas Jefferson University Hospital is consistently ranked in the top 50 best hospitals for treating cancer in America (#31 in 2011) in U.S. News and World Report. What’s more, the hospital has moved up more than 20 places in the past five years for cancer.



A Tumor Suppressor May Also Fight Obesity

The hormone receptor guanylyl cyclase C (GCC) has been established as a suppressor of colorectal cancer tumors, but new evidence from Thomas Jefferson University suggests it may also help fight one of the country’s biggest pandemics: obesity.

Reporting in the August 25 online issue of the Journal of Clinical Investigation, Scott Waldman, M.D., Ph.D., chairman of the Department of Pharmacology and Experimental Therapeutics at Jefferson, and colleagues 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.

Revealing a never-before-shown endocrine axis between the intestine and hypothalamus, the research could provide novel therapeutic targets to control appetite, obesity and the metabolic syndrome, a promising notion, given that one-third of the U.S. population is considered obese.

Until now, the role of GCC outside the gut has remained elusive. Dr. Waldman and his team have previously shown its role as a tumor suppressor and biomarker that reveals occult metastases in lymph nodes. But its role in appetite is new and surprising territory.

“We were working with GCC-deficient mice to look at its role in tumorigenesis in the intestine,” said Dr. Waldman.  “Then the mice grew up, and we noticed something: They got fatter.

“We couldn’t understand why it was happening, because GCC is expressed predominantly in intestine, and there was no indication that it regulated any function that had to do with metabolism and nutrient uptake.”

To investigate this, Dr. Waldman, who also leads the Gastrointestinal Malignancies Program at the Kimmel Cancer Center at Jefferson, and his colleagues raised both GCC mice and GCC deficient mice, tracking their weight, satiation responses, hepatic and serum triglyceride measurements, hormone receptor expression, and physical activity.

When food was digested by the mice, they found, the gut released hormones into the blood stream, not just within the intestines, and up into the brain, where the hormone receptors were triggered. Mice with GCC knew when to stop, but hormone receptor-deficient mice never got the message that their stomachs were full. They simply kept eating and became obese.

“They got to be diabetic and developed the metabolic syndrome, fatty livers, etc.” Dr. Waldman said. “We ruled out usual suspects: gastroenterology function was normal. They weren’t more sedentary than wild type mice. And they did not have abnormal metabolism. We realized they just have a different appetite.”

The research offers up a new neural-gut axis that explains appetite more, but it still begs some questions: Do obese people possess little to no GCC? And if so, does that mean obese people have a genetic disposition to gain weight?

It’s possible, said Dr. Waldman, but it’s still unclear. There is the possibility that obese people do not have the receptor or they do not release enough hormones to trigger the receptor. More studies are needed to better explain this, he added.

“Obesity could be biological, and not behavioral,” said Dr. Waldman. “But there is no evidence here that confirms that; however, knowing this new information opens that possibility.”



Jefferson Clinical Trial: Can a Cholesterol Drug Prevent Colon Cancer?

Thomas Jefferson University has started recruiting patients for a new National Cancer Institute (NCI)-sponsored clinical trial to test whether the cholesterol-reducing drug rosuvastatin is effective in the prevention of recurrent colon cancer.

Previous laboratory research and population studies have shown that patients taking statins, the class of drugs that lowers cholesterol, had fewer colon polyps, which can lead to cancer if left untreated. However, those findings come largely from retrospective, observational studies originally designed to investigate lipid-lowering or cardiovascular endpoints in the short term rather than tumor endpoints.

“The jury is still out, and we need to get definitive answers,” said Bruce Boman, M.D., Ph.D, professor of medical oncology at Thomas Jefferson University and principal investigator for the national clinical trial. “This prospective design comparing a statin against a placebo is what is needed to address the question: Are statins effective chemoprevention agents or not?”

This five-year, nationwide study will be the first randomized, prospective, placebo-controlled, double-blind study to evaluate the drug’s role in preventing colon cancer and will involve 1,740 patients in total.

Conducted by a network of cancer research professionals from the National Surgical Adjuvant Breast and Bowel Project (NSABP) at 400 medical centers across North America, including Jefferson, the study involves patients who have recently been diagnosed with early stage colon cancer, and who were not already taking statins for high cholesterol.  Those recruited have been surgically treated for stage I and II colon cancers previously.

Patients will be randomly assigned to one of two groups.  Each group will take one pill a day for five years.  One group will receive rosuvastatin, while the other group will receive a placebo.

The cumulative incidence for developing colorectal adenomas three years after surgery/treatment for early stage colon cancer is 50 percent. Thus, the benefit/risk ratio for chemoprevention intervention is potentially very positive in this high-risk population.

“There will be an estimated 102,900 new cases of colon cancer in the United States this year,” said Norman Wolmark, M.D., NSABP’s chairman.  “In fact, colorectal cancer is the third most common cancer found in men and women in this country.   We hope this trial will be an important step in reducing these numbers.”

The principal investigator for the trial at Jefferson is Scott Goldstein, M.D, director of the Division of Colon and Rectal Surgery at Thomas Jefferson University.

People recently diagnosed with a Stage I or II colon cancer and interested in the study should contact Vicki Squire of Thomas Jefferson University at  Vicki.Squire@jeffersonhospital.org or 215-503-5641.

A list of other sites in North America that are participating in the study may be found at http://www.nsabp.pitt.edu/P5_Sites.asp



Shifting a paradigm: A molecular approach to staging colorectal cancer

A quantitative, molecular analysis of lymph nodes in patients deemed colorectal cancer-free was found to be an effective predictor of recurrence, according to a study from researchers at the Kimmel Cancer Center at Jefferson and published online Feb 9. in Clinical Cancer Research.

Recurrence occurs in about 25 percent of node-negative patients (pN0), suggesting that occult metastases escaped detection, be it imaging modalities or histopathology.

To better predict recurrence and accurately stage these patients, Terry Hyslop, Ph.D. and Scott A. Waldman, M.D., Ph.D. of the Department of Pharmacology and Experimental Therapeutics of Thomas Jefferson University and the Kimmel Cancer Center at Jefferson, and colleagues explored a novel molecular approach, using the biomarker GUCY2C for metastatic colorectal cancer cells.

Using 291 colorectal cancer patients who were node-negative, the researchers analyzed lymph nodes by histopathology and GUCY2C quantitative qRT-PCR. They were followed for a median of 24 months and categorized as having either low, intermediate or high tumor burdens.

The researchers had previously concluded that expression of GUCY2C increased risk of recurrence. However, it is apparent that nodal metastases do not assure recurrence; rather they indicate risk.

The researchers found that patients with greater occult tumor burden have a greater risk of recurrence compared to patients with less burden. Thus, molecular tumor burden in lymph nodes are independently associated with time to recurrence and disease-free survival in patients with node-negative colorectal cancer.

“This approach can improve prognostic risk stratification and chemotherapeutic allocation in pN0 patients,” the authors write. “More generally, this study reveals a previously unappreciated paradigm to advance cancer staging, clinically translating emerging molecular platforms that complement histopathology, laboratory diagnostic, and imaging modalities.”



Giovanni M. Pitari, M.D., Ph.D. receives award from the American Institute for Cancer Research

Giovanni M. Pitari, M.D., Ph.D., has received an award from the American Institute for Cancer Research to support his research project entitled ‘Therapeutic Synergy between Dietary Calcium and Bacterial Enterotoxins for the Prevention and Treatment of Colon Cancer’. The award provides research funding directed toward discovering innovative therapeutic modalities for cancer prevention and cure. Dr. Pitari is Associate Professor in the Department of Pharmacology and Experimental Therapeutics and Director of the Laboratory of Investigative Medicine at TJU.



Second Annual Get Your Rear In Gear Event

The second annual Philadelphia Get Your Rear In Gear will took  place at 7:30 a.m. on Martin Luther King Drive in Philadelphia, Sunday, March 21, 2010, during National Colorectal Cancer Awareness Month.  Both survivors and those lost to colorectal cancer were honored.  There was a 5K Race  and a 2 mile Remembrance Walk.

Results are available at getyourrearingear.com

Below are pictures from the Kick-Off Meeting:



Pre-emptive Treatment Helped Curtail Skin Toxicity with Panitumumab

Dr. Edith Mitchell

Dr. Edith Mitchell

With a pre-emptive, prophylactic skin regimen, patients who receive panitumumab for treatment of metastatic colorectal cancer may be able to avoid some of the skin-associated toxicities, according to data presented at the 2009 American Society of Clinical Oncology Gastrointestinal Cancers Symposium in San Francisco.

Edith Mitchell, M.D., a clinical professor in the Department of Medical Oncology at Jefferson Medical College of Thomas Jefferson University, presented data from the study, which was the first prospective study to compare pre-emptive and reactive skin treatment for skin toxicities related to panitumumab. The study was co-led by Dr. Mitchell and Mario Lacouture, M.D., an assistant professor of Dermatology at Northwestern University’s Feinberg School of Medicine in Chicago.

Read more…



African-Americans Have Worse Prognosis Compared to Caucasians When Diagnosed With Colorectal Cancer

Dr. Edith Mitchell

Dr. Edith Mitchell

African-American patients with colorectal were more likely to present with worse pathological features at diagnosis and to have a worse five-year survival rate compared to Caucasian patients, according to a study conducted by researchers at Thomas Jefferson University.

The results are being presented at the 2009 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium. The study was led by Edith Mitchell, M.D., a clinical professor in the Department of Medical Oncology at Jefferson Medical College of Thomas Jefferson University. Dr. Mitchell is also associate director of Diversity Programs for the Kimmel Cancer Center at Jefferson.

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Different Type of Colon Cancer Vaccine Reduces Disease Spread, Jefferson Scientists Show

Taking advantage of the fact that the intestines have a separate immune system from the rest of the body, scientists at the Kimmel Cancer Center at Jefferson in Philadelphia have found a way to immunize mice against the development of metastatic disease.

Reporting online Tuesday, June 24, 2008 in the Journal of the National Cancer Institute, Scott Waldman, M.D., Ph.D., professor and chair of Pharmacology and Experimental Therapeutics at Jefferson Medical College of Thomas Jefferson University and his co-workers have shown that mice immunized with an intestinal protein developed fewer lung and liver metastases after injection with colon cancer cells than did control animals that were not immunized. The work may portend the development of a different kind of cancer vaccine, the researchers say, that may help prevent disease recurrence.

Read more…