Conquest - Fall 2008

CONQUEST F A L L

The heart of the matter Cardiology team breaks new ground

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MISSION The mission of The University of Texas M. D. Anderson Cancer Center is to eliminate cancer in Texas, the nation, and the world through outstanding programs that integrate patient care, research and prevention, and through education for undergraduate and graduate students, trainees, professionals, employees and the public.

VISION We shall be the premier cancer center in the world, based on the excellence of our people, ÂŽ

our research-driven patient care and our science. We are Making Cancer History .

C O R E   VA L U E S

Caring By our words and actions, we create a caring environment for everyone.

Integrity We work together to merit the trust of our colleagues and those we serve.

Discovery We embrace creativity and seek new knowledge.

On the cover: Juan Carlos Plana, M.D., assistant professor in the Department of Cardiology and director of Cardiac Imaging, and Liza Sanchez, supervisor of the Cardiovascular Lab, view a 3-D echocardiogram. The specially designed glasses allow them to see the heart in three dimensions, giving them the opportunity to accurately define cardiac structure and function.

Tiffany Hebert Spinos survived not only two cancers but also heart failure caused by the lifesaving treatments. Today, her husband and baby daughter own her heart. Tiffany is profiled in a Conquest online special feature.

Visit the Conquest Internet site at www.mdanderson.org/conquest

Features

CONTENTS C O N Q U E S T

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Deeppartment a r t m e n tss D

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2 FRONTLINE Turning on CB1 Slowing down metastatic thyroid cancer Looking long term Shielding a metastasis-promoter

6 Brain boost $11.5 million grant supports personalized therapy The SPORE score: 11 and counting

Diabetes drug may serve as anti-tumor agent

8 The heart of the matter 14 Symptom research Old drugs, new possibilities Interventions to relieve symptom burden enter clinical trials

As they gain a deeper understanding of the effect of cancer treatments on the heart, a full-service cardiology team is breaking new ground treating cancer patients.

18 Profile: Lois Ramondetta, M.D. 22 Cancer briefings On top, again New sister in Hong Kong Cattlemen for Cancer Research passes $1 million mark

24 Moving Forward Gordon Hendrickson Pancreatic and prostate cancer patient counsels others

A gynecologic oncologist offers unconventional care through meaningful conversations with patients at M. D. Anderson and Harris County Hospital District’s Lyndon B. Johnson General Hospital.

21 ‘Sew’ easy: Onesies keep toddlers safe A physician assistant has adapted a common article of infant clothing to protect young cancer patients’ central lines.

CONQUEST | Fall 2008

FRONTLINE Turning on CB1 Cannabinoids may provide new approach for colorectal cancer prevention, treatment New preclinical research shows that cannabinoid cell surface receptor CB1 plays a tumor-suppressing role in human colorectal cancer.

CB1 is well established for relieving pain and nausea, elevating mood and stimulating appetite by serving as a docking station for the cannabinoid group of signaling molecules. It now may serve as a new path for cancer prevention or treatment.

“We’ve found that CB1 expression is lost in most colorectal cancers, and when that happens a cancer-promoting protein is free to inhibit cell death,” says senior author Raymond DuBois, M.D., Ph.D., provost and executive vice president of M. D. Anderson.

DuBois and collaborators from Vanderbilt-Ingram Cancer Center also show that CB1 expression can be restored with an existing drug, decitabine. They found that mice prone to developing intestinal tumors that also have functioning CB1 receptors develop fewer and smaller tumors when treated with a drug that mimics a cannabinoid receptor ligand.

Ligands are molecules that function by binding to specific receptors. Agonists are synthetic molecules that mimic the action of a natural molecule.

“Potential application of cannabinoids as anti-tumor drugs is an exciting prospect, because cannabinoid agonists are being evaluated now to treat the side effects of chemotherapy and radiation therapy,” DuBois says. “Turning CB1 back on and then treating with a cannabinoid agonist could provide a new approach to colorectal cancer treatment or prevention.”

Cannabinoids are a group of ligands that serve a variety of cell-signaling roles. The body produces some internally. External cannabinoids include man-made versions and those present in plants, most famously the active ingredient in marijuana.

Reported in the Aug. 1 issue of the journal Cancer Research.

Image source: The RCB ProtEIn Database

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Raymond DuBois, M.D., Ph.D., was the senior author on a study that may lead to new paths for colorectal cancer prevention or treatment. The study was funded by grants from the National Cancer Institute and the National Colorectal Cancer Research Alliance.

[ frontline ] Slowing down metastatic thyroid cancer

Thyroid cancer that has spread to distant sites has a poor prognosis. But an experimental drug that inhibits tumor blood vessel formation can slow disease progression in some patients, a research team led by M. D. Anderson investigators reports.

The investigational drug, motesanib diphosphate, is a VEGF inhibitor, a biologic agent that targets receptors on a protein known as vascular endothelial growth factor.

VEGF is instrumental in angiogenesis (formation of new blood vessels), a process that allows tumors to grow and spread.

Of the 93 patients with rapidly progressing cancer who were enrolled in the study, 49 percent had a positive response. From that group 14 percent had their tumors shrink and 35 percent had their tumors stabilize for more than 24 weeks. Median progression-free survival was estimated to be 40 weeks.

Study lead author Steve Sherman, M.D., chair of M. D. Anderson’s Department of Endocrine Neoplasia and Hormonal Disorders, noted strong evidence that VEGF receptors play an important role in metastatic thyroid cancer, a disease with few treatment options.

Genetic analyses of 25 patients indicated that those with a specific mutation known as BRAF V600E in their tumors had a better response to motesanib diphosphate than did those without the mutation. Additional research is needed on this genetic connection, but the early results are a good start, Sherman says.

“There’s no standard accepted chemotherapy for advanced metastatic differentiated thyroid cancer, and response rates have typically been 25 percent or less,” Sherman says. “Most patients are not treated with systemic chemotherapy because the limited benefit rarely justifies the side effects.”

“There’s no standard accepted chemotherapy for advanced metastatic differentiated thyroid cancer, and response rates have typically been 25 percent or less.”

— Steve Sherman, M.D.

Reported in the July 3 issue of The New England Journal of Medicine.

Sherman, colleagues in 10 countries and scientists from Amgen, which is developing motesanib diphosphate (AMG 706), planned and conducted one of the largest clinical trials ever done for metastatic thyroid cancer.

Steve Sherman, M.D., chair of the Department of Endocrine Neoplasia and Hormonal Disorders, headed a study that may lead to improved treatments for patients with metastatic thyroid cancer.

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CONQUEST | Fall 2008

FRONTLINE Looking long term Risk assessment strategies can pay off

Breast cancer patients and their physicians may make more informed, long-term treatment decisions using risk assessment strategies to help determine probability of recurrence, according to a research team led by M. D. Anderson scientists.

The 2,838 women studied were diagnosed with stage I-III breast cancers and had been treated between 1985 and 2001 with adjuvant systemic therapy, such as chemotherapy and/or tamoxifen, and were in the M. D. Anderson Tumor Registry. They also were five years past the start of this therapy and were cancer-free.

Researchers calculated the residual or remaining risk of recurrence using the benchmark of five years from the start of AST. They also determined the factors that contributed to a higher residual risk of recurrence.

“Understandably, one of the most common questions posed by breast cancer survivors is ‘What are the chances of it coming back?’” says the study’s lead author, Abenaa Brewster, M.D., assistant professor in M. D. Anderson’s Department of Clinical Cancer Prevention. “Now we can tell some women within a certain percentage their future risk of recurrence and clinicians may be able to make more informed decisions regarding prescription of extended adjuvant endocrine therapy.”

Data analysis revealed that 89 percent of the study population didn’t experience a recurrence at five years (approximately 10 years after a woman’s initial diagnosis), and 80 percent didn’t experience a recurrence at 10 years (approximately 15 years after diagnosis).

While this is reassuring for most of the five-year survivors, the percentage of the population who had a recurrence is significant to oncologists, Brewster says.

“The magnitude of risk of recurrence should indicate a need for us to consider extended endocrine treatment for eligible women to further lower their risks,” she says.

Reported in the Aug. 12 online issue of the Journal of the National Cancer Institute.

The results of a study led by Abenaa Brewster, M.D., assistant professor in the Department of Clinical Cancer Prevention, will help better determine the risk of breast cancer recurrence for some women.

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[ frontline ] Shielding a metastasis-promoter Efforts to protect the tumor-suppressor p53 could just as easily shelter a mutant version of the protein, causing cancer cells to thrive and spread rather than die, according to research by M. D. Anderson scientists.

“As we develop therapies to restore the function of p53, we need to make sure we first know what version of this gene is present in a patient’s tumor and then decide how to treat it,” says senior author Guillermina Lozano, Ph.D., chair of M. D. Anderson’s Department of Genetics.

The research shows that attempting to restore normal expression of p53 protein by blocking another protein that normally degrades p53 can have the reverse effect of protecting mutated p53 and promoting metastasis.

The p53 gene is inactivated in many types of cancer.

Its normal role is to halt the division of a defective cell and then force the cell to kill itself or deprive the cell of its ability to reproduce. Reactivation of p53 is thought to have great therapeutic potential.

Normally, p53 levels are low, but it springs into action in response to DNA damage or activation of cancer-promoting genes, or oncogenes.

Guillermina Lozano, Ph.D., chair of the Department of Genetics, stresses the importance of knowing which version of p53 is present in a patient’s tumor before treating it.

Reported in the May 22 issue of the journal Genes & Development.

Diabetes Drug may serve as anti-tumor agent Metformin, the common first-line drug for type 2 diabetes, may be effective in increasing pathologic complete response rates in diabetic women with early-stage breast cancer who took the drug during chemotherapy prior to having surgery.

According to M. D. Anderson researchers, this will pave the way for further research of the drug as a potential cancer therapy.

The retrospective study is the first clinical research observation of the diabetes drug as a potential anti-tumor agent. The study was led by Sao Jirlerspong, M.D., Ph.D., a fellow, and Ana Gonzalez-Angulo, M.D., an assistant professor, both in M. D. Anderson’s Department of Breast Medical Oncology.

Metformin, an oral medication, is the most common drug prescribed for type 2 diabetes. According to Gonzalez-Angulo, more than 35 million prescriptions of the drug are filled annually. It’s most often given to diabetic patients who are obese or have insulin resistance.

Reported june 2 during the 2008 annual meeting of the American Society of Clinical Oncology.

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CONQUEST | Fall 2008

W.K. Alfred Yung, M.D. (left), and Oliver Bogler, Ph.D., are co-principal investigators on M. D. Anderson’s $11.5 million Specialized Programs of Research Excellence grant for brain tumor research from the National Cancer Institute.

BRAIN BOOST $11.5 million grant supports personalized therapy In 2008, it’s expected that nearly 22,000 new cases of brain or central nervous system tumors will be diagnosed.

And, according to the National Cancer Institute, about 13,000 people will die from brain malignancies.

With support from a five-year, $11.5 million Specialized Programs of Research Excellence grant from the NCI, M. D. Anderson researchers hope to take a bite out of those statistics.

The brain tumor SPORE builds on institutional expertise in several departments. Funds from the translational research grant will help advance two new therapeutic approaches for malignant brain tumors, including glioblastoma multiforme, and develop biomarkers to guide treatment decisions.

“All four of the projects funded by this grant apply molecular and genetic approaches to develop new targeted therapies and biomarkers that will improve treatment by personalizing therapy,” says W.K. Alfred Yung, M.D., chair of the Department of Neuro-Oncology and co-principal investigator on the SPORE with Oliver Bogler, Ph.D., associate professor in the Department of Neurosurgery.

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[ spore grants ]

Project 1: Deploying a tumor-killing virus The engineered adenovirus Delta-24-RGD, developed at M. D. Anderson, will advance to clinical trial, and a second-generation version will be developed as a single therapy and in combination with other drugs. Delta-24 will be injected directly into tumors during a Phase I clinical trial that’s under review at the U.S. Food and Drug Administration.

Principal investigators: Juan Fueyo, M.D., associate professor, Department of Neuro-Oncology; Frederick Lang, M.D., professor, Department of Neurosurgery.

Project 2: Blocking a malignant pathway Drugs that block a molecular signaling cascade known to fuel brain tumors — the PI3K pathway — will be developed and tested in Phase I trials. Individual targeted molecules and rational drug combinations will be studied for their potential to inhibit PI3K. Principal investigators: Garth Powis, D.Phil., chair, Department of Experimental Therapeutics; W.K. Alfred Yung, M.D., chair, Department of Neuro-Oncology; Oliver Bogler, Ph.D., associate professor, Department of Neurosurgery.

Project 3: Identifying treatment guideposts Researchers are developing and validating a set of genes that predict survival and sensitivity to treatment for glioblastoma patients. This biomarker approach to sorting out personalized treatment is being conducted in collaboration with clinical trials testing a variety of therapies and combinations for glioblastoma.

Principal investigators: Kenneth Aldape, M.D., professor, Department of Pathology; Howard Colman, M.D., Ph.D., assistant professor, Department of Neuro-Oncology.

Project 4: Pinpointing genetic role in brain impairment By analyzing the genetic makeup of glioblastoma patients and relating it to the type and degree of cognitive impairment they experience after radiation treatment, researchers aim to identify and understand genes that affect cognitive outcomes.

Principal investigators: Melissa Bondy, Ph.D., professor, Department of Epidemiology; Christina Meyers, Ph.D., professor, Department of Neuro-Oncology.

The SPORE score: 11 and counting When it comes to SPOREs, M. D. Anderson has no peers The Specialized Programs of Research Excellence grant for brain tumor research marks the 11th such award M. D. Anderson has received from the National Cancer Institute — the most held by any institution.

“This award marks a very significant event for M. D. Anderson and indicates the important role that the institution plays in the field of translational research,” says Raymond DuBois, M.D., Ph.D., provost and executive vice president. “We’re essentially leading the way in developing multidisciplinary research teams to accelerate the transition of basic knowledge into the clinic.”

M. D. Anderson’s other SPORE grants are in leukemia and melanoma as well as breast, genitourinary, pancreatic, ovarian, uterine, head and neck, prostate and lung cancers. The lung SPORE is shared with The University of Texas Southwestern Medical Center in Dallas.

Cancer Type Brain

Total Funding

. . . . . . . . . . . . . . . . . . . $11.5 million

Breast . . . . . . . . . . . . . . . . . . . $11.9 million Genitourinary . . . . . . . . . . . . . . . $26.6 million Head and neck . . . . . . . . . . . . . . . $13.7 million Leukemia . . . . . . . . . . . . . . . . . . $23.9 million Lung

. . . . . . . . . . . . . . . . . . . $12.8 million

Melanoma. . . . . . . . . . . . . . . . . $11.2 million Ovarian . . . . . . . . . . . . . . . . . . . $23.8 million Pancreatic. . . . . . . . . . . . . . . . . . $4.9 million Prostate. . . . . . . . . . . . . . . . . . . $13.6 million Uterine . . . . . . . . . . . . . . . . . . . $9.6 million Total . . . . . . . . . . . . $163.5 million

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CONQUEST | Fall 2008

The heart of the matter

Cardiology team breaks new ground treating cancer patients

Edward T.H. Yeh, M.D., chair of the D epartment of Cardiology, is leading a growing team of clinicians and basic scientists that is defining the role of cardiology in cancer care.

by Julie Penne

It takes a lot of heart to battle and live with cancer.

But when patients have to confront both cancer and heart disease — still the top two leading causes of death in Americans today — they need a full-service cardiology team that knows cancer and an oncology group that respects the impact that many lifesaving cancer therapies can have on the heart.

At M. D. Anderson there are both.

“Cardiology has a unique place at M. D. Anderson, and as we successfully treat more and more people for their cancer, we know that some patients’ hearts are weakened or damaged,” says Edward T.H. Yeh, M.D., founding chair of the Department of Cardiology. “This presents a conundrum for our team, but it’s also an obligation to protect our patients’ hearts, expand our research and build a new discipline in cardiology. In many ways, we liken cardiology in the cancer setting now to what cancer prevention was two decades ago, and, certainly, M. D. Anderson was a pioneer in that field of study.”

As the only comprehensive cardiology department at any cancer center, M. D. Anderson’s clinic has more than doubled the number of patients seen in the last eight years. In 2000, three cardiologists and two physician assistants saw about 1,700 patients in the clinic and made about 3,700 visits to hospitalized patients. Today, with 10 cardiologists, two physician assistants and four advanced practice nurses, more than 4,900 patients are seen in the clinic and more than 7,300 inpatient consultations are done. In 2000, there were more than 38,500 inpatient and outpatient procedures performed — chiefly EKGs and echocardiograms — while this year, approximately 75,000 procedures will be done.

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In this painting Titled “SUMO and SENP1 wrestling over the Goddess of Hypoxia (HIF1α),” artist Julie Newdoll depicts research published by Edward YeH, M.D., in The Journal Cell in 2007.

The Goddess of Hypoxia or HIF1α stands on a high mountain peak, where the air is thin or hypoxic, and sends out newly formed blood vessels from her gown and blood cells from her sleeves. SUMO is attempting to wrestle the goddess to throw her to the lurking dragon, which is proteasome. SENP1, armed with a sword, is trying to attack SUMO, separating him from the goddess and saving her from the dragon. The SUMO character is based on wall paintings from the North Dynasties, representing figures practicing the Chinese Sumo-like martial art Shuai Chiao. The SNEP1 character on the far right was inspired by Guan Yu, the Chinese god of war who lived during the three kingdom era. The Goddess of Hypoxia is modeled in part on Guan Yin, the Chinese Goddess of Mercy, and the mountain peaks are inspired by the Yellow Mountains of China. This painting hangs in Yeh’s administrative office.

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CONQUEST | Fall 2008

Isaam Raad, M.D. (left), chair of the Department of Infectious Diseases, Infection Control and Employee Health, and Jean-Bernard Durand, M.D., associate professor in the Department of Cardiology, compare experiences with the antibiotic-coated pacemaker (pictured on page 11) that has helped decrease the infection rate among patients who get the device. Raad developed the coating more than a decade ago, and Durand now implants the pacemakers in patients with severe heart failure. (See related article below.)

Don’t lose heart — There’s good news The increase in patients is due to a variety of factors, notes Yeh and other faculty. Unanimously, they report the increased use of a class of chemotherapies, known as anthracyclines, and the new targeted therapies as the primary reason for the increase in patients with cardiac damage and, when left untreated, heart failure.

While highly effective in the treatment of many cancers, some of these drugs were found to cause hypertension and induce heart failure. Though not all patients receiving this class of drugs are affected, the rate can be significant.

For example, bevacizumab (Avastin) causes hypertension in 23 percent to 34 percent of patients and is life threatening in 14 percent. Other common chemotherapies that can induce heart failure include bortezomib (Velcade), trastuzumab (Herceptin) and sunitinib (Sutent).

“We have found that some patients will survive their cancers but die from heart disease exacerbated or caused by the therapies,” says Daniel Lenihan, M.D., professor in the Department of Cardiology. “It’s vital that we get in at the beginning of patients’ treatments to make sure their hearts are strong. But it’s also important that we monitor

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Infection fighter: Coating developed at M. D. Anderson hugs pacemakers When Jean-Bernard Durand, M.D., began using a new type of pacemaker earlier this year to reduce the risk of infection, he switched to a device that was enveloped in a clear antibiotic coating. Little did he know until several months later that the drug combination used in the protective sleeve was invented by an M. D. Anderson colleague — and it worked.

Durand was not satisfied with the 2 percent infection rate among his patients getting pacemakers. Though 2 percent is considered low in a general hospital setting, he was concerned that any infection could be serious for patients and delay their continuing cancer therapy.

[ CARDIOLOGY ]

these patients throughout their treatment because the good news, in all this not-so-good news about these therapies, is that we can treat and often reverse these heart conditions.”

According to Jean-Bernard Durand, M.D., associate professor in the Department of Cardiology and one of the original three faculty, a beta blocker or ACE (angiotensin converting enzyme) inhibitor are often the most effective therapies for treating heart failure. For more severe cases, he says, a pacemaker or other options may be considered. (See related article below.) Durand founded the cardiomyopathy services at M. D. Anderson, the first heart failure service at a cancer hospital.

Another valuable tool in assessing how the heart will hold up in treatment is echocardiography. This evaluation technique measures certain heart functions, including the calculation of “ejection fraction,” a numeric measurement of how effectively the heart is pumping on each beat.

Measuring risk early As one way to get ahead of heart problems as early as possible, or better yet to prevent them altogether, M. D. Anderson cardiologists are studying a simple blood test called the BNP, or brain natriuretic peptide, that could predict heart failure in some patients. Results of a patient’s BNP are an early indication of cardiac dysfunction caused by cancer treatments. Plus, they help guide both cardiologist and oncologist toward the optimal treatment program.

In addition to examining all other possible risks for infection, Durand turned his attention to using a pacemaker coated in an anti-bacterial envelope.

The same device that’s implanted in the chest to regulate a heart beat, this pacemaker has a coating that slowly disintegrates into the body and releases antibiotics to fight infection.

After a few procedures with the new pacemaker and noting the decline in infection rates, Durand mentioned the new device to Isaam Raad, M.D., chair of the Department of Infectious Diseases, Infection Control and Employee Health at M. D. Anderson, who also was pleasantly surprised that his invention had been adapted for use with pacemakers and was contributing to positive infection control. According to Durand’s initial observations, the new pacemaker is yielding zero infections thus far.

Though he sold the rights to his concept and formula about 10 years ago, Raad originally developed and adapted the antibiotic drug combination for central line and urologic catheters, major points of entry for infection for cancer patients. Thousands of these coated catheters are in use every day throughout M. D. Anderson and the United States.

“I knew Dr. Raad would be thrilled that we were reducing the rates of infection among our pacemaker patients, but he was even more enthusiastic when he heard that it was due in great part to his antibiotic scaffolding,” Durand says. “It’s great to be using a product that’s not only effective but also homegrown.”

The antibiotic-coated pacemaker envelope is manufactured by TyRx Pharma Inc., of Princeton, N.J. — Julie Penne

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CONQUEST | Fall 2008

“It’s imperative that we’re precise in reporting findings to our oncology colleagues regarding ejection fraction because it’s evidence of how the heart is reacting to cancer treatment,” says Juan Carlos Plana, M.D., assistant professor in the Department of Cardiology and director of Cardiac Imaging.

“In many instances, it’s this test that determines what type of treatment will be given to a patient or if a lifesaving chemotherapy can be continued.”

In addition to following patients who have chemotherapy-induced heart failure or high blood pressure, the cardiology team monitors and fortifies a growing number of patients for cancer treatment or surgery. These are people with pre-existing heart conditions, high blood pressure or high cholesterol or those who have had recent surgery such as bypass or valve repair. In addition, the cardiology team often consults with the surgical and anesthesia teams regarding patients who may have stents and are taking the necessary blood-thinning medications.

Community cardiologists to see more survivors What distinguishes M. D. Anderson cardiologists from community cardiologists is that they treat patients with two serious diseases at the same time, Lenihan says.

But as the number of survivors increases, community cardiologists could see many more cancer survivors who have lingering heart conditions.

That’s why the cardiology team is working to establish collaborations with community cardiologists and other cancer centers, to present more cancer-related studies at national cardiology meetings, to publish more cardiology studies in peer-reviewed oncology journals and to push for more attention to the increasing cardiology needs of cancer patients.

Later this year, one of cardiology’s major organizations, the Heart Failure Society of America, is expected to publish guidelines for more standardized yet aggressive treatment of cancer patients and survivors.

Read the details of It’s a major step towards bringcancer and heart patient ing more awareness to the many Tiffany Hebert Spinos’ compelling story online at www.mdanderson.org/conquest.

Cath lab a fundamental at all major hospitals, A vital novelty at M. D. Anderson Come early next year, M. D. Anderson patients needing more thorough cardiac evaluations and some procedures will be able to stay on campus and be treated by the team they know and who knows them.

In January, M. D. Anderson will open a diagnostic catheterization lab, the first cath lab to operate at a cancer center in the United States.

Similar to the common technology at any major hospital in the United States, M. D. Anderson’s cardiac catheterization lab will be used in the first year chiefly to perform diagnostic procedures and conduct research. First proposed about five years ago as a

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fundamental step in advancing cardiology and patient care, the department projects completing more than 300 diagnostic procedures in the first six months of operation.

Leading the project is Cezar Iliescu, M.D., assistant professor in the Department of Cardiology, who came to M. D. Anderson in June from The University of Texas Health Science Center at Houston. Iliescu, who rotated through M. D. Anderson as part of his cardiology fellowship, was struck by the innovative care and the opportunity to work with major influencers in cancer and cardiac care.

[ CARDIOLOGY ]

needs of cancer patients and survivors who also suffer with heart ailments and the need for more research.

Cardiology cross-pollinates with nearly every service at M. D. Anderson and has worked on translational research projects with other clinical departments. The department also has a strong basic research program on both cancer and heart disease. For example, Yeh’s group discovered a crucial link between hypoxia, or low oxygen, and cancer, and collaborates with M. D. Anderson oncologists to use adult stem cells to treat heart disease.

“This is an exciting time to be working in cardiology and cancer, and there are many who are anxiously watching our patient care and research programs progress,” Yeh says. “What we do today and in the years to come has the potential to touch millions of lives, not just at M. D. Anderson but all over the world, and we welcome newcomers to the field we are creating.”

growing up in Colombia, Juan Carlos Plana, M.D., remembers vividly his mother coming to M. D. Anderson for treatment of lymphoma. Today, she is cancer-free, but comes to Houston for follow-up appointments, and to visit her son and his family.

“In addition to enhancing the care of our patients, the cath lab will open up new opportunities for cardiac research that’s cancer specific,” Iliescu says. “We’ll be able to see coronary heart disease from the inside and better understand how cancer influences heart disease and vice versa.”

In the past eight years, as needs for cardiac care and diagnostics have increased, M. D. Anderson cardiologists have been forced to transfer patients to neighboring hospitals and hand off their care temporarily to colleagues who know hearts but who don’t have extensive experience with the hearts of cancer

patients. It’s a traumatic and difficult decision for both M. D. Anderson cardiologists and patients.

“It’s very difficult to tell patients and their families that we don’t have the technology to do an important test when they have come to the best cancer center in the world,” says Daniel Lenihan, M.D., professor in the Department of Cardiology. “For the physician, it’s tough to turn a patient over to another team, and it’s hard for the patient to leave a comfortable environment.

Having our own cath lab truly will revolutionize how we care for our patients.”

— Julie Penne

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[ SYMPTOM RESEARCH ]

Old drugs, new possibilities Soon an antibiotic, an antidepressant, a spice and a wakefulness-promoting agent may be tested in various combinations as treatments for five specific cancer-related symptoms: fatigue, pain, sleep disturbance, lack of appetite and drowsiness.

by Sandi Stromberg

Curcumin, derived from Curcuma longa, is the main ingredient of the common yellow spice turmeric. Curcumin has properties that make it an excellent candidate for symptom control. In animal models, curcumin has been shown to safely suppress pain, depression and exercise-related functional impairment.

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CONQUEST | Fall 2008

Under the guidance of Charles Cleeland, Ph.D. — the ever-diligent detective who has spent his career tracking cancer-related symptoms and assessing clues to unlock their mystery — interventions may be as close as a combination of these four tried-and-true agents.

While his early investigations centered on pain, in the last few years, he and his colleagues in the Department of Symptom Research have widened their search to include other symptoms. They also have involved other health care professionals across M. D. Anderson: first, to identify symptoms that are general to all cancer patients and, then, to ascertain which are particular to specific types of cancer.

Based on their findings in patients with head and neck cancers and non-small cell lung cancer, they recently received federal funding to plan two randomized clinical trials, which will aim to test combinations of antibiotics and other agents, including curcumin (a component of the spice turmeric) to reduce the severity of cancer treatment-induced symptoms.

“It’s an exciting opportunity,” says Cleeland, chair of the Department of Symptom Research and principal investigator on the renewal of this National Cancer Institute grant. “One of the problems with symptom research to date has been the lack of a strong evidence base. We’ve been working in somewhat of a vacuum. Now we have the funding to get good clinical trial information about a general and very accessible approach to symptoms.”

Charles Cleeland, Ph.D., is the principal investigator on a research program that will study the effects of combinations of treatments on the severity of treatment-related symptoms in patients with lung and head and neck cancers. The studies, funded by the National Institutes of Health, will use common treatment agents and novel statistical approaches to identify the most effective treatment combinations.

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[ SYMPTOM RESEARCH ]

A constellation of impacts

The clinical trials will continue the work Cleeland and his symptom researchers began several years ago with clinical investigators David I. Rosenthal, M.D., professor and director of Head and Neck Translational Research, and Zhongxing Liao, M.D., associate professor, both in the Department of Radiation Oncology.

Together, they defined the specific symptoms patients with these cancers experience in response to treatment, creating two of the M. D. Anderson symptom inventories, the MDASI-HN (head and neck) and the MDASI-Lung.

“These patients start off with very few or no symptoms at diagnosis,” Cleeland says.

“Then, from chemoradiation they develop a constellation of symptoms that we’ve learned are associated with very aggressive cancer therapy. These can cause significant distress and are poorly controlled despite standard supportive care.”

Growing scientific evidence suggests that symptoms occur in clusters and that common biologic mechanisms, such as inflammatory cytokines (signaling proteins), may cause or contribute to these clusters. Cleeland’s group hopes that by investigating various combinations of these drugs with broad anti-inflammatory properties and low toxicity, it will be able to reduce the most severe symptoms caused by these treatments: fatigue, pain, sleep disturbance, lack of appetite and drowsiness (in lung cancer patients) or difficulty swallowing (in head and neck cancer patients).

Not only is this symptom burden unpleasant for patients, but it also can jeopardize their job and, subsequently, their health benefits. Some symptoms may become so severe that patients need a treatment “holiday” or must completely discontinue treatment.

Area under the curve “One of the novel things about this study is that we’re picking five of the most frequent and severe symptoms that we’ve uncovered in our earlier studies and with these agents aiming for what we call an ‘area under the curve,’” Cleeland says.

In the proposed clinical trials, researchers will track the impact that interventions have over a period of time, using an interactive voice response system. A computer will call patients who, using their telephone keypad, will self-report the severity of their symptoms on a scale of 0-10, 0 being “not present” and 10 being “as bad as you can imagine.”

By charting responses, Cleeland and his group will know that treatment is successful if the peak in symptom severity is reduced. For example, if overall fatigue drops from a 5 to a 2 (on the 0-10 scale) over time, this will be reflected in the area under the curve.

Comparing the areas under the curve for two treatments will give a clear indication of which treatment better reduces patients’ symptom burden (see figure on page 17).

The lower the area under the curve, the more successful the treatment.

“While this is a pretty familiar concept,” Cleeland says, “the unusual thing is that we plan to apply it to symptoms.”

Cancer survivors know best what the side effects of cancer and its treatments are. Yet, they often lack the words to describe what they feel and the appropriate tools for self-reporting. Gathering symptom-related data to improve survivors’ daily lives is the central focus of M. D. Anderson’s Department of Symptom Research.

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CONQUEST | Fall 2008

Average AUC Comparison of 5 SYmptoms by Type of Treatment in Patients with HNC

Old becomes new

Nyma Shah, program manager in the Department of Symptom Research, collects symptom information during a patient interview. Patients provide the same symptom information from home using a computerized, telephone-based interactive response system.

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Average Symptom Severity

Unlike curative cancer treatments, symptom-focused treatments are rarely tested in combination. Now, the two proposed trials will allow Cleeland and his team the unique opportunity to evaluate the effectiveness of combining therapies.

“After a certain point in time, when everything has been tested a little, additional patients will be assigned to the study treatment, depending on how each agent or combination of agents is. It’s somewhat like running a Phase I-II trial,” Cleeland says.

This approach is possible because the trials will use the Bayesian adaptive randomization design instead of the classic randomized clinical trial approach. Valen Johnson, Ph.D., professor and deputy chair of the Department of Biostatistics, developed the design for this novel approach to treatment assessment, the first of its kind to be used in a clinical trial based on patient report of symptom severity.

Chemotherapy combined with radiation Radiation only

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Time Point in Weeks This area under the curve (AUC) provides a telling visual representation of a comparison of two treatments (chemotherapy combined with radiation versus radiation only) as reflected in the severity of five symptoms (pain, fatigue, sleep disturbance, lack of appetite and difficulty swallowing). Over 11 weeks of treatment, patients receiving radiation therapy alone reported less severe symptoms than the patients receiving the combination therapy, indicated by the smaller AUC. The Bayesian design allows for smaller, more informative trials. As results about the effectiveness of each agent or agent combination accumulate, they can be incorporated into the study and patients can be assigned to the treatments that are the most effective.

Less successful treatments will be dropped. Continual comparing and recomparing of treatments throughout the course of the trial should eventually whittle the possible combinations of treatments down to only those that are the most effective for reducing symptoms.

In addition, due to the minimal toxicities and interactions that these agents have with one another, the method also makes it possible to assign multiple treatments to the same patients.

“The exciting thing for me is that the more we can do here, the better,” Cleeland says. “It used to be that the side effects of therapies were so horrible you sort of closed your eyes and treated. Doctors at M. D. Anderson have a sense now that symptoms can be treated, and as our co-investigators they want to help patients in a way that leaves them with less symptom burden.”

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[ PROFILE: Lois Ramondetta, M.D. ]

Since 2000, Lois Ramondetta, M.D., assistant professor in the Department of Gynecologic Oncology, has worked two days a week at Lyndon B. Johnson General Hospital in Houston. She operates a clinic on Wednesdays and performs surgery on Thursdays. M. D. Anderson partners with the hospital, a component of the Harris County Hospital District, to provide specialized oncology care at the facility in keeping with its commitment to the citizens of the state of Texas. She is pictured with uterine cancer patient LaToysha Fernandez.

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CONQUEST | Fall 2008

Unconventional care through meaningful conversations

by Nada El-Sayed

For Lois Ramondetta, M.D., caring for patients goes beyond the conventional doctor-patient relationship, whether she’s seeing patients at M. D. Anderson or at Harris County Hospital District’s Lyndon B. Johnson General Hospital in Houston.

As associate professor in the Department of Gynecologic Oncology, her focus is on having open conversations with her patients and building a stronger rapport with each encounter.

“I try to get to know people so that each time a person comes to the clinic it ends up being a real visit,” she says. “I try to figure out what I can do to help. It’s through those conversations that I find out what gives meaning to a patient’s life. Then I’m able to help her make more informed decisions about what, often times, especially with ovarian cancer, is going to be a terminal illness.”

Creating a relationship with her patients helps Ramondetta go beyond what is generally expected of physicians. It also helps her bring up more delicate issues, like spirituality, which has led to some of her research studies.

“Sometimes, if you let yourself, all you do is go in and do the exam. You say ‘hi’ and ‘bye’ and that’s it. You think, ‘I just had a woman come in to see if she had a recurrence or not’ and then it’s done. There’s no connection. I think doctors have to be careful not to let that happen.”

Personal treatment for the underserved In Fiscal Year 2000, Ramondetta became part of M. D. Anderson’s initiative that has committed staff to underserved patient populations at Harris County’s LBJ General Hospital. With other parttime clinical faculty members, oncology fellows and research nurses, she works side by side with hospital district employees in both the outpatient gynecological cancer clinic and the inpatient service.

“It’s a very warm clinic about the size of two of these rooms,” she says, motioning around her office. “It has three stalls, walls that don’t go to the ceiling and no doors, just curtains. But there’s always a lot of hugging and laughing. Also, I think the continuity of seeing the same doctors and nurses each time is really good for the patients. It’s very rewarding and personable.”

Another part of her work at LBJ is to conduct clinical treatment trials as well as study the psychological and social barriers to care so prevalent in this patient population.

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[ PROFILE: Lois Ramondetta, M.D. ] Books sheds light on ‘living a bigger life’

“Last year, we did a survey assessing anxiety, depression and sexual dysfunction in patients who came through the clinic and found huge levels of sexual dysfunction,” she says. “Now, Mary Hughes, an advanced practice nurse in the Department of Psychiatry, comes out to LBJ four hours a week to see our patients.”

Ramondetta also has collaborated with Charles Cleeland, Ph.D., chair of the Department of Symptom Research, and Eduardo Bruera, M.D., chair, Department of Palliative Care and Rehabilitation Medicine, focusing on palliative care, pain and symptom management to determine who in this patient group might be eligible for clinical trials.

“The Light Within,” a book co-authored by Lois Ramondetta, M.D., and a former M. D. Anderson ovarian cancer patient, Deborah Rose Sills, Ph.D., tells the story of the doctor-patient relationship the two shared.

Written in two voices, it describes two perspectives of dealing with cancer. One is that of Sills, who was being treated for ovarian cancer; the other is of the physician, Ramondetta.

“Someone asked me what I think Deb would want women to know from the book, and I think it’s that cancer is not a gift,” Ramondetta says. “Certainly not a gift, but with every challenge there is opportunity and that opportunity allows for this existential growth as a human being with relationships. It’s an opportunity for living a bigger life than you were living before.”

Spirituality: How it affects her medical practice While Ramondetta has published numerous articles on her clinical research, she says, “The aspect of oncology that is really interesting to me is the whole conversation about what really gives meaning to our lives.”

In the article she co-wrote with Deborah Rose Sills, Ph.D., “Spirituality in Gynecological Oncology: A Review” (published in the International Journal of Gynecological Cancer, March-April 2004), she discusses how reproductive cancers undermine a patient’s identity as a woman and the connection between the healing of the body and the spirit.

“Religion cannot answer ‘how’ questions, and science cannot answer ‘why’ questions. What religionists and scientists-physicians share and what they share with all human beings is the knowledge that all of us ‘will surely die,’” she writes.

Having grown up with no formal religious education, her interest in the study of religion and spirituality didn’t begin until her undergraduate years at Emory University. First, she learned the basics of the Old and New Testaments. Those eventually led her into the Unitarian Universalist realm.

“In school, I was studying biology and religion and couldn’t decide which to major in,” she says.

She also participated in a lay chaplaincy program, which she describes as “six months of learning how to listen.”

“I think that was actually a great course for any medical student,” she says. “I really learned how to do some medical journaling about the people I met and then learned how to reflect on that.”

Her research in the past few years has helped her learn to cope more with what is happening to her patients, while helping her learn how they cope.

“I don’t know why, but dealing with patients who are facing a potentially terminal illness as well as being able to do research on spirituality has helped me continue my ongoing attempt to understand those unanswerable questions.

“I’m fascinated with the people I meet, especially at the county hospital, who reflect on their illness in such a way that is filled with a strength that I think I’ll never have. I’m fascinated to the point that I almost wish I could believe as strongly as they believe because what happens in the end happens to all of us.”

See more of Ramondetta’s story in Conquest online at www.mdanderson.org/conquest.

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CONQUEST | Fall 2008

‘Sew’ easy: Onesies keep toddlers safe

by Sara Farris

“Don’t touch.”

Those two words rarely make an impression on any toddler. They can have even less effect on young cancer patients with central lines, whose need to touch and tug often causes these lines to pull loose or come out.

To remedy the issue, Holly Green, a surgical physician assistant from the Children’s Cancer Hospital at M. D. Anderson, discovered a unique way to adapt a common article of infant clothing to protect these lines.

While central lines make it easier to administer chemotherapy over time, whenever they come out, a pediatric patient must have additional surgery to replace the line, costing thousands of dollars. With each new line or port, obtaining access to the veins becomes more difficult for surgeons, and patients are left with multiple external scars and scarring of the veins.

Discovery: a core value at work “I came up with the idea after a young patient pulled out his central line seven times in one year,” says Green, who has been a physician assistant for 20 years. “It’s stressful for the entire family any time a 2-year-old has to go into surgery, even if it’s for a minor procedure.”

Using her sewing skills, Green was able to modify a “onesie,” a one-piece cotton garment for babies, that would keep their hands from reaching the central line. Volunteers from Green’s church then took her pattern and have sewn a special opening in the back of more than 200 of these outfits.

The hole allows the central line to wrap around and exit at the patient’s back, out of a toddler’s reach.

This special outfit comes in different sizes, fitting patients from 6 months to 4 years old.

The Children’s Cancer Hospital treats nearly 100 infant and toddler patients each year, so the new garment is very useful.

Funding to produce the garments was provided through a safety grant that Green received from the Physician Assistant Foundation.

Physician Assistant Holly Green stops by to check on a pediatric patient who is wearing Green’s creation, a special onesie designed to protect toddlers from pulling out their central lines.

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CONQUEST | Fall 2008

CANCER BRIEFINGS

Cattlemen for Cancer Research passes $1 million mark

Cattlemen for Cancer Research broke the $1 million mark in total funds raised at its 10th annual cattle auction in October benefiting M. D. Anderson’s Department of Veterinary Sciences.

This year, the Bastrop, Texas, based grassroots organization raised $140,000 for a total of $1.01 million for cancer research at the institution’s Michale E. Keeling Center for Comparative Medicine and Research in Bastrop.

The organization contributes a portion of auction proceeds to a patient assistance fund that helps local residents with transportation and living expenses. For the past six years the event has honored a cancer survivor who has benefited from that fund. This year all past and present honorees shared the spotlight.

The event includes a silent auction, a luncheon and then the auction of more than 40 cattle. This traditionally includes the repeated sale of several head of cattle as buyers donate them back for resale.

Three generations of Keelings take in the 2007 Cattlemen for Cancer Research auction near Bastrop, Texas: Clyde Keeling (left), his grandson Doug Keeling and greatgrandson Garrett. Clyde is the father of the late Michale Keeling, M.D., founding director of the Michale E. Keeling Center for Comparative Medicine and Research in Bastrop; Doug is Michale Keeling’s son and Garrett is his grandson.

The 2008 auction brought the total raised in the auction’s 10-year history to more than $1 million.

“I’m proud of the way the agriculture community has come together to support M. D. Anderson and the work that they do,” says Brenda Cardwell, who’s worked on the Cattlemen for Cancer Research committee for nine years, serving as president for three years.

“The organization has grown each year through the hard work of people who really care about making a difference for those who suffer from cancer now and those who will suffer from this disease in the future,” says Christian Abee, D.V.M., director of the Keeling Center and chair of the Department of Veterinary Sciences.

— Scott Merville

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[ cancer briefings ]

On top, again For the fourth time in the past six years, M. D. Anderson is the nation’s top hospital for cancer care according to U.S. News & World Report’s annual “America’s Best Hospitals” survey.

M. D. Anderson has been ranked as one of the top two hospitals for cancer care every year since the survey began 19 years ago.

“I am very proud that M. D. Anderson has again been recognized for its outstanding patient care, innovative clinical trials program, nursing, supportive services,

Anthony T.C. Chan, M.D., director of the cancer center at the Chinese University of Hong Kong; Karen Fields, M.D., vice president for global academic programs at M. D. Anderson; and Tai Fai Fok, M.D., dean, faculty of medicine, chinese university of Hong Kong, sign a formal agreement between the two institutions at a press conference.

community outreach and research,” says M. D. Anderson President John Mendelsohn, M.D. “Every day, our faculty, staff and volunteers live our mission to eradicate cancer, and this honor recognizes their relentless efforts. We share this with all of our courageous patients who are both our inspiration and driving force in Making Cancer History®.”

M. D. Anderson specialties earning additional national rankings also include ear, nose and throat (4); urology (9); gynecology (16); and pediatrics (21).

The U.S. News & World Report rankings are based on a reputation survey of board-certified physicians around the nation, patient discharge data and a mix of care-related factors such as nurse-to-patient ratios, current technologies and services available to patients and the community.

New sister in Hong Kong M. D. Anderson and the Sir Y.K. Pao Centre for Cancer and Hong Kong Cancer Institute at the Chinese University of Hong Kong have signed a sister institution agreement that formalizes existing collaboration in research and patient care and expands the scope of our joint efforts.

“The Chinese University of Hong Kong has renowned clinical and academic research programs and remarkable therapeutic expertise,” says John Mendelsohn, M.D., president of M. D. Anderson. “The new partnership will create and support more opportunities for innovative cancer research collaborations to ultimately reduce the incidence of cancer and suffering among patients globally.”

Cancer is the number one cause of death in China. In 2005, approximately 1,892,000 people died from cancer and the number of new cases is increasing at a rapid rate.

The institutions have identified nasopharyngeal carcinoma, hepatocellular carcinoma and glioma as initial research areas of focus. The collaboration aims to establish a clinical trial network among China, East Asia and M. D. Anderson, and educational exchange programs for post-graduate students, clinical fellows and oncology nurses with training opportunities at CUHK. To date, M. D. Anderson has established sister institution relationships with 18 premier academic and clinical cancer centers around the world.

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[ moving forward ]

Moving Forward: Gordon Hendrickson

As a survivor of both pancreatic cancer and prostate cancer, Gordon Hendrickson is compelled to counsel other men and women about screening and to help those who are newly diagnosed.

“I was in good health. It never dawned on me I might develop cancer,” says Hendrickson. He was 66 in May 2002 when he heard the life-changing diagnosis of pancreatic cancer.

Hendrickson asked his internist to locate the best surgeon who could perform the recommended Whipple procedure, a complicated operation that involves removing parts of the pancreas as well as portions of the stomach and small intestines, adjacent lymph nodes, gallbladder and part of the common bile duct. The internist found M. D. Anderson has several specialists with extensive experience and increasingly good results.

Fortunately, he was a successful candidate for the Whipple procedure and is now a six-year survivor of that disease. And he is about to celebrate the two-year anniversary of his prostate cancer.

These experiences make him an apt spokesman, counseling others to pay attention to their health. In Albuquerque, where he and his wife, Nancy, live, he

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facilitates a men’s group for People Living Through Cancer, a program that brings together those who understand the physical, mental, emotional and spiritual repercussions of cancer.

“In my work with this group, I have found that those who catch the cancer early have the best chance of a good outcome,” Hendrickson says. “I encourage everyone to get a colonoscopy, especially if they are over 40 and if they aren’t feeling well. I also encourage all men to have their PSA monitored.”

Inveterate travelers, he and his wife journey around the country, staying off the freeways so they can enjoy the sights, while visiting their five children and eight grandchildren.

“We feel so fortunate to have a large family and so many friends,” he says. “Like others who have survived a critical event or disease, we know how important these people are in our lives.”

affiliations

The University of Texas System Board of Regents

M. D. Anderson Cancer Center Orlando, Orlando, Fla. Centro Oncológico M. D. Anderson International España, Madrid, Spain M. D. Anderson Clinical Care Center in the Bay Area, Nassau Bay, Texas M. D. Anderson Radiation Treatment Centers in Bellaire, Fort Bend, Katy and The Woodlands, Texas; and Albuquerque, N.M. Christus Spohn Stem Cell Program affiliated with M. D. Anderson Cancer Center Outreach, Corpus Christi, Texas

H. Scott Caven, Jr., Houston Chair

James Richard Huffines, Austin Vice Chair

Robert B. Rowling, Dallas Vice Chair

John W. Barnhill, Jr., Brenham James D. Dannenbaum, Houston Paul Foster, El Paso Printice L. Gary, Dallas

Stephen C. Stuyck, Vice President for Public Affairs

Janiece M. Longoria, Houston

Sarah Newson, Associate Vice President for Communications

Colleen McHugh, Corpus Christi

Executive Editor:

Benjamin L. Dower, Dallas

David Berkowitz, Director of Publications and Creative Services

Student Regent

Managing Editor: Sandi Stromberg, Program Manager of External Publications

Francie A. Frederick General Counsel

The University of Texas System Administration

Kenneth I. Shine, M.D.

Writers: David Berkowitz, Nada El-Sayed, Sara Farris, Scott Merville, Julie Penne, Mary Jane Schier, Sandi Stromberg Designer: Michael Clarke

Chancellor Ad Interim

The University of Texas M. D. Anderson Cancer Center EXECUTIVE COMMITTEE

John Mendelsohn, M.D. President

Thomas W. Burke, M.D.

Executive Vice President and Physician-in-Chief

Raymond N. DuBois, M.D., Ph.D.

Photographers: Wyatt McSpadden (cover, inside front cover, Contents, pages 3, 4, 5, 6, 10, 11, 12, 13, 21), Jake Schoellkopf (page 24), F. Carter Smith (Contents, pages 2, 8, 9, 14, 15, 16, 17, 18, 20, garment-page 21), Cattlemen for Cancer Research (page 22) Photo Editor: Brenda K. Gunter

Provost and Executive Vice President

Leon J. Leach

Executive Vice President

The University Cancer Foundation Board of Visitors OFFICERS

Ernest H. Cockrell Chair

Marc J. Shapiro

Conquest is published quarterly by The University Cancer Foundation Board of Visitors on behalf of The University of Texas M. D. Anderson Cancer Center. All correspondence should be addressed to the Division of Public Affairs-Unit 229, M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, 713-792-3457. E-mail: sfstromb@mdanderson.org.

Articles and photos may be reprinted with permission.

For information on supporting programs at M. D. Anderson Cancer Center, please contact Patrick B. Mulvey, Vice President for Development, 713-792-3450, or log on to the Development Office Internet site at www.mdanderson.org/gifts.

Immediate Past Chair

Nancy B. Loeffler Chair-Elect

Ali A. Saberioon Vice Chair

For information on patient services at M. D. Anderson, call askMDAnderson at 1-877-MDA-6789, or log on to www.mdanderson.org/ask.

V i s i t t h e C o n q u e s t I n t e r n e t s i t e a t w w w. m d a n d e r s o n . o r g /c o n q u e s t . © 2008 Not printed at state expense.

Printed on recycled paper with soy-based ink.