A Comprehensive Cancer Center Designated by the National Cancer Institute

Pathways to Discovery: Summer 2010

Feature Articles
Volume 5 | Number 2

  1. Customized Approach Advances Cancer Care
  2. Finding Tumor 'Signature' Could Offer New Treatment Possibilities
  3. Pediatric Specialists Strive to Reduce the Side Effects of Radiation Therapy
  4. Persistence, Ingenuity Create Unrivaled Head and Neck Cancer Program
  5. Michigan Communities Rally to Support Endowed Fund for Neuroblastoma Research

Customized Approach Advances Cancer Care

The Department of Radiation and Cellular Oncology is committed to improving cancer care through clinical and basic science research. Many cancer patients undergoing treatment receive radiation therapy to shrink and destroy their tumors. Led by Ralph Weichselbaum, MD, chair and D.K. Ludwig Professor of Radiation and Cellular Oncology, researchers are deciphering how cells respond to radiation to improve the effectiveness of radiation therapy.

"We are applying basic discoveries in the laboratory to the clinical arena. Our mission is to improve the treatment of early stage tumors by decreasing radiation toxicity and to expand the role of radiation therapy to treat patients with cancers that are very difficult to cure," explained Dr. Weichselbaum.

An integrated team of radiation oncologists and physicists is designing and delivering the most targeted and customized radiation therapy options for patients based on these basic laboratory discoveries. Multidisciplinary care is an important aspect of successful treatments. Radiation therapy is frequently combined with chemotherapy and surgery.

Faculty in the department conduct broad basic research programs, including those that focus on DNA repair, cell signaling, gene therapy, and medical physics. For example, researchers in medical physics, led by Charles Pelizzari, PhD, are developing new image-guided approaches to precisely target and assess the response of tumors to radiation. David Grdina, PhD, MBA, recently discovered how enzymes that detoxify free radicals may protect normal tissues from radiation toxicity. Also, Stanley Liauw, MD, found that patients with prostate cancer respond better to radiation therapy when using cholesterol-lowering medications. These research findings are quickly making their way into experimental clinical trials.

Dr. Weichselbaum, who specializes in the treatment of patients with advanced malignancies, also conducts a dynamic research program in his laboratory. He is testing radiation-induced gene therapy in clinical trials, identifying the interaction between radiation and the immune system, exploring how specific drugs can accelerate the aging process in cancer cells, and defining how some tumors are resistant to radiation therapy. "The idea is to be able to profile gene expression in a patient's tumor and determine how it may or may not respond to therapy so that we can devise an individualized treatment plan," said Dr. Weichselbaum.

The department places a major research emphasis on the treatment of patients with metastatic cancer. Metastasis is the leading cause of cancer deaths because tumor cells are frequently resistant to treatment after traveling from the site of origin to other organs. Dr. Weichselbaum discovered that an intermediate state, called oligometastasis, exists between early stage cancer and cancer that has spread extensively.

"We have shown in clinical trials that patients with five or fewer discrete sites of metastasis can be safely treated with high-dose radiation when standard therapies have failed," explained Dr. Weichselbaum. Researchers are now searching for molecular biomarkers to identify patients with oligometastasis and for ways to sensitize tumors to radiation therapy.

"UChicago is a leader in radiation oncology because of the exceptional quality of our faculty. Our researchers are smart, creative, hard-working, and committed to delivering scientifically advanced, personalized care to our patients," according to Dr. Weichselbaum.

Finding Tumor 'Signature' Could Offer New Treatment Possibilities

Now that we have the technology, what we want to know now is, "Can we identify something from a patient's cancer that can help us customize cancer treatment?"
—Steven J. Chmura, MD, PhD

Steven J. Chmura, MD, PhD, is an award-winning researcher, clinician, instructor, mentor, and UChicago graduate, but his most rewarding accomplishment has been treating patients.

"The changes I have seen over the past few years in the technology, knowledge, and the evolution of cancer treatment have been astounding. To follow a patient through to see them cured and leading a good quality of life is the absolute best," said Dr. Chmura, an assistant professor of radiation and cellular oncology, head of the radiation oncology residency program, and principal investigator of the Radiation Trials Oncology Group (RTOG) at UChicago.

Dr. Chmura is involved with several clinical research trials on both the local and national levels. His current focus is persuading the National Cancer Institute to support a national protocol through RTOG that could help change the course of treatment for women with breast cancer.

"Conventional wisdom suggests that if breast cancer has spread, localized treatment of those areas of disease would not be effective. The standard of care is to employ chemotherapy or hormone treatment, but this course of therapy is not expected to be curative," explained Dr. Chmura. "We now have the technology to deliver very high doses of targeted radiation to the disease in any part of the body while avoiding normal tissue."

Using this therapy, called stereotactic body radiation therapy (SBRT), along with hypofractionation—large doses of radiation targeted to a precise area—UChicago cancer treatment teams have been able to reach lesions in many locations that cannot be reached surgically, such as deep inside the liver or critical organs, with relatively few complications.

Along with Joseph K. Salama, MD, and others, Dr. Chmura published initial data in 2008 showing favorable toxicity, feasibility, and long-term outcomes using hypofractionated SBRT. As other large academic centers are now duplicating the results, Dr. Chmura is taking the next step, "Now that we have the technology, what we want to know now is, 'Can we identify something from a patient's cancer that can help us customize cancer treatment?'"

If researchers can determine a cancer's genetic "signature" and associate the signature with response to therapy, then cancer treatment teams may be able to predict, for example, which cancer is a slow-progressing disease or which one will respond to surgery, chemotherapy, or radiation therapy.

"To do this on a national level for breast cancer and not only assess how many women can be helped, but also which patients can be helped, is very powerful," he said. A similar trial is under way at UChicago for lung cancer.

"We have a great advantage here because we can harness the power of the academic environment in translational research and integrate this into the best possible patient care," said Dr. Chmura. "Ultimately we have the most state-of-the-art technology to treat our patients, we ensure that treatment is done correctly, and we surround our patients with a welcoming staff to help them get through their course of treatment."

Pediatric Specialists Strive to Reduce the Side Effects of Radiation Therapy

Pediatric specialists at The University of Chicago are improving treatment options for patients with childhood cancers. Today, nearly 80% of children diagnosed with cancer survive because of significant advances in cancer treatment. Children treated at UChicago benefit from a multidisciplinary approach that combines the expertise of pathologists, radiologists, pediatric surgeons, and pediatric medical and radiation oncologists.

Philip Connell, MD, associate professor of radiation and cellular oncology, is an expert in pediatric radiation oncology who treats approximately 50 pediatric patients each year, as well as adult patients with soft tissue sarcomas or thoracic cancers. "Radiation therapy can be used to treat a wide range of pediatric cancer types," said Dr. Connell. "The pediatric oncology program is known for its expertise in treating both common and very rare forms of pediatric cancers. The most common types of pediatric solid tumors treated with radiation therapy at UChicago include neuroblastoma, brain tumors, and sarcomas."

UChicago participates in the Children's Oncology Group (COG), a National Cancer Institute-supported research group whose mission is to study childhood cancers and improve therapies. A major initiative of the COG is to improve the outcome of radiation therapy while reducing its side effects. "One of the key differences between radiation therapy for pediatric versus adult patients is that kids are much more susceptible to radiation-induced side effects," said Dr. Connell. While radiation therapy can successfully treat some cancers, it can cause serious long-term side effects. In brain tumors, for example, radiotherapy comes with the risks of hearing loss, cognitive problems, and developmental delays, especially in the youngest children.

Specialists at UChicago use state-of-the-art radiation technologies, including intensity-modulated radiation therapy (IMRT) and image-guided radiation therapy (IGRT), to reduce the likelihood of these side effects. "IMRT uses sophisticated computer algorithms to optimize the intensity within each beam of radiation," explained Dr. Connell. "Treatment is delivered via multiple beams at variable intensities and angles, rather than through beams in front and back of the tumor, as performed in more basic methods of radiation therapy. This technology often allows us to escalate doses of radiation to precisely attack the tumor while minimizing damage to normal surrounding tissue."

In addition to treating patients, specialists in the pediatric radiation oncology program are focused on research to improve treatment options. UChicago is recruiting patients to approximately 100 different pediatric clinical trials, many of which are testing radiation in combination with other types of treatment such as chemotherapy or surgery. For example, a child may receive radiation therapy to shrink a tumor during or prior to being given an experimental drug as part of a clinical trial.

Dr. Connell also conducts laboratory-based research to develop new drug therapies that can either sensitize cancer cells to chemotherapy and radiation or protect normal tissues from these treatments. He is particularly interested in developing pharmacologic agents that target RAD51, a protein that plays a central role in repairing DNA double strand breaks that occur when cells are exposed to radiation.

"If we can develop a compound that protects normal tissue from the effects of toxic drugs or radiation, then we can support a central mission of the COG, which is to reduce the toxicity of therapies. Likewise, if we can develop a drug that specifically sensitizes tumors to therapies, then theoretically, this may allow us to reduce the intensity of radiation or chemotherapy without lessening cure rates," explained Dr. Connell.

The pediatric radiation oncology program at UChicago continues to expand its faculty and expertise and improve its radiation technology capabilities. "As radiotherapy technologies continue to improve, we will be able to shield healthy tissues even better and minimize the side effects of radiation therapy," said Dr. Connell.

Persistence, Ingenuity Create Unrivaled Head and Neck Cancer Program

I like being able to tell people who come in with untreated Stage 4 head and neck cancer that we have a 70%-80% chance of curing them.
—Daniel J. Haraf, MD, MS

Patient accrual begins soon for a clinical trial that may forever change the way radiation therapy is delivered.

Right now, when patients are treated for head and neck cancer, radiation is targeted to areas where the cancer is, as well as to areas where the cancer is believed to be. The new trial is a joint effort of medical oncology, otolaryngology, and radiation oncology that will investigate whether radiation is needed in those suspicious areas if the patient has responded well to chemotherapy.

"Our new trial will restrict the amount of radiation therapy that will be used," said Daniel J. Haraf, MD, MS, medical director of radiation oncology and professor of radiation and cellular oncology. "We are just going to treat the known area of disease which will save the patient a lot of toxicity."

The head and neck cancer program at UChicago is world-renowned for combining innovative chemotherapy, radiation therapy, surgery, and skill to save organs that other cancer teams never thought could be saved.

"Here at UChicago we are 'myth busters'," said Dr. Haraf. "We are dispelling through our own data and our own experience things that people have held as the standard for a long time. We were told you can't give chemotherapy and radiation therapy to a patient with a large cancer of the larynx because that patient will never eat or talk again. Guess what? The naysayers were wrong."

Two other myths the team has dispelled are that patients cannot be treated with chemotherapy and radiation therapy if the cancer has grown into the bone, and that the tongue cannot be saved if the patient has tongue cancer.

One beneficiary of the head and neck cancer team's tenacity and ingenuity is world-famous Chicago chef Grant Achatz, who was given a 40% chance of survival and was told by two other medical institutions that he needed radical surgery to treat his tongue cancer. Achatz opted for treatment at UChicago, where combined chemotherapy and radiation therapy not only saved his life, but also saved his tongue.

Data are now being analyzed on two recently completed clinical trials. One trial will add more information to the debate over whether chemotherapy provides greater benefit when administered as neoadjuvant (induction, that is prior to radiation) therapy or concurrently with radiation therapy.

The second clinical trial involves the timing of chemotherapy and radiation therapy. "One way is the way we do it at the UChicago—on alternate weeks," he explained. "The other way is a method that is used by a national group where all outpatients start out receiving once-a-day radiation and finish with twice-a-day treatment."

As Dr. Haraf awaits the final data analysis of the recently completed studies, he takes pride in two recently published studies—one, in the June 2010 issue of Radiotherapy & Oncology, describes his team's success in using chemo-reirradiation for recurrent salivary gland malignancies; the second, published online and to appear in an upcoming print issue of Head & Neck, describes the outcomes of base-of-tongue cancers treated with chemoradiotherapy.

"I like both of these papers for different reasons. Few people were willing to do second rounds of radiation therapy when I started this," he said. "Reirradiation is the only chance of survival for many of these patients. The second paper reports some of the best treatment results for patients with advanced base-of-tongue cancer without surgery to remove the tongue."

"I like being able to tell people who come in with untreated Stage 4 head and neck cancer that we have a 70%-80% chance of curing them," Dr. Haraf continued. "I've kept in touch with many of my patients over the years. They send me Christmas cards and photos of their children. I've treated or consulted with patients from every continent of the world, except for Antarctica."

Dr. Haraf credits teamwork for the success he's enjoyed over the years. "What makes us different at UChicago is that we have a dedicated head and neck cancer team that includes medical oncologists, radiation oncologists, and surgeons. These are quality people who do it right."

Michigan Communities Rally to Support Endowed Fund for Neuroblastoma Research

We hope and pray our work will benefit many neuroblastoma and pediatric cancer patients.
—Ellie Bittker

Stroll through West Bloomfield, Michigan, on a pleasant summer afternoon, and you might be puzzled by the number of people wearing apparel featuring the theme, "It's What Matters." If you journey to Birmingham, Franklin, or other nearby communities, you could encounter the same phenomenon.

"It's What Matters" plays on the name of Matthew Bittker, a compassionate young child who was diagnosed with stage 4 neuroblastoma during the 2006 Super Bowl weekend and died from the malignancy 18-months later at the age of 6. Neuroblastoma is a cancer of immature nerve cells that affects mostly infants and children.

Sweatshirts, T-shirts, and other logo merchandise help celebrate Matthew's life and raise money for pediatric cancer research with an emphasis on neuroblastoma. The apparel also symbolizes the extraordinary response of the local community and efforts made by Matthew's parents, Allan and Ellie, and their three remaining children—twins Jason and Susie and Matthew's twin Elana—to support cancer research, spread awareness of neuroblastoma and pediatric cancer, and to remember Matthew's courage, empathy, and joyfulness.

Ellie designs the apparel, then she, her family and friends work tirelessly to extend the reach of the Matthew Bittker Foundation. The foundation has already made a difference, providing a $100,000 endowment to support Susan Cohn, MD, professor of pediatrics and director of clinical research in the Section of Hematology/Oncology at The University of Chicago. Dr. Cohn is a globally recognized expert in pediatric cancers and a leading authority on neuroblastoma. She is one of the few pediatric oncologists in the U.S. who is conducting Phase I clinical trials of promising treatments for the disease.

The foundation also keeps alive Matthew's charm and compassion. "Throughout his treatment, Matthew was aware and sympathetic of the sufferings of others," Ellie said. "He would say how horrible the child in a wheelchair or elderly woman bent over by disease must feel."

Matthew's sympathy and friendliness charmed many adults and children. He remained lively and joyful throughout the course of his battle with cancer, even after he was told that the tumor had returned. By year's end, his foundation will have raised almost $250,000 and the community has been instrumental to the foundation's success.

"Matthew would have been thrilled by the tremendous response of our friends and the community," said Allan. "Many people of all ages have volunteered to help promote and support the foundation's endeavors.

They have engaged schools, stores, summer camps, and sororities to help raise much needed funds." Even Matthew's baseball league got into the game. Franklin Baseball purchased more than 300 red shirts for their annual all-star game with the slogan "Franklin Baseball: It's What Matters." Matthew loved playing baseball, and the foundation's logo is a baseball cap with a blue (his favorite color) ribbon.

More than 200 merchants participate in another fundraising activity for the foundation. The "Shop4aCure Card" program entitles holders to a 20% discount at a diverse range of national and local stores, such as Ralph Lauren, California Pizza Kitchen, and Guys N Gals. With the support of the Somerset Collection (a luxury retail center in Southfield, Michigan) and a small army of volunteers to sign merchants and sell cards, the community comes together to help Matthew's foundation. The foundation retains all proceeds from card sales.

The foundation's success is based on Matthew's character and personality. "His spirit inspires us to work tirelessly to build a living tribute to our warm-hearted son who touched so many in his short life. We hope and pray our work will benefit many neuroblastoma and pediatric cancer patients," Ellie explained. "We look forward to providing additional grants to fund critically needed pediatric cancer research."

Learn more about Matthew, the Matthew Bittker Foundation, and the Bittker family at itswhatmatters.org

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