Conquest - Fall 2007

CONQUEST F

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V O L U M E

HOPE IS ON THE HORIZON

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I S S U E

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M I S S I O N 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.

V I S I O N We shall be the premier cancer center in the world, based on the excellence of our people, 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: Kelly Stewart feels on top of the world these days after an investigational drug she’s been taking has put her disease in remission.

Check out the Conquest Web site at w w w. m d a n d e r s o n . o r g / c o n q u e s t

CONTENTS C O N Q U E S T

FALL 2007

F E AT U R E S

4 2 FRONTLINE BATTLE-ing Lung Cancer

HOPE IS ON THE HORIZON

Hodgkin’s lymphoma patients, whose disease has relapsed despite frontline therapies, now have more choices to find

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SYMPTOM RESEARCH

a treatment that works.

Measuring the Immeasurable

11 SURGERY SPARES FERTILITY

A radical surgical procedure is giving women with cervical

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PROFILE

cancer the possibility of maintaining their fertility while

Janet M. Bruner, M.D. treating the disease.

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MOVING FORWARD Robert Dorsey Jr.

FINDING ANSWERS IN THE LOST PINES

Scientists at the Virginia Harris Cockrell Cancer Research Center have been unraveling the origins of cancer from their unique rural Texas surroundings for 30 years.

CONQUEST FALL 2007

FRONTLINE BATTLE-ING LUNG CANCER In a novel project matching drugs to molecular targets in lung cancer, M. D. Anderson investigators are engaging in an intensive and ongoing interrogation of the tumors themselves.

The underlying premise of the landmark package of clinical trials — known collectively as the Biomarkerbased Approaches of Targeted Therapy for Lung Cancer Elimination — is to let the biology of a patient’s tumor teach physicians how to treat that tumor. A major step toward individualized therapy, BATTLE examines four treatment options against biomarkers representing four molecular pathways that fuel lung cancer, and relies heavily on core biopsies of patients’ tumors before and during the trial.

Despite the approval of new drugs in recent years, lung cancer remains stubbornly difficult to treat and is the leading cause of death due to cancer, says Edward Kim, M.D., assistant professor in M. D. Anderson’s Department of Thoracic/Head and Neck Medical Oncology and BATTLE clinical trial principal investigator.

“We have no targeted therapies for lung cancer,” he says. “There’s been a tunnel vision approach to research, with clinical trials focusing on a single drug and a single biomarker. Those trials are costly, and often they don’t pan out. We’re broadening our approach.”

In the BATTLE study, patients with previously treated, advanced non-small cell lung cancer are randomly assigned to one of four treatment options.

They are evaluated eight weeks after treatment begins.

If the cancer remains stable or has improved, they stay on the first treatment. Patients whose disease has progressed may drop out of their initial study arm and enter one of the other studies of a drug that targets a different molecular pathway.

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As the four clinical trials progress under the BATTLE umbrella, investigators evaluate disease progression and changes in the genomic profiles of the tumors after treatment via follow-up biopsies. Information from early patients in the trial gradually influences which treatment may be best for later patients, a unique adaptive randomization study design that learns as it goes.

“Patient accrual is like a ramp,” Kim explains. “As the statistical model learns from each patient enrolled in the study, assignment to a treatment arm becomes more targeted and less random. As we learn more about which biomarkers respond best to which drugs, more patients will go on a treatment arm favoring that biomarker.”

As the trial progresses, the number of patients enrolled in a treatment arm may increase or decrease, or a treatment arm might be discontinued.

Using this approach, investigators are trying to “understand the biologic properties of tumor tissue, to detect a dominant tumor progression pathway and then to give the right agent to block that molecular pathway, seeing whether it correlates with tumor response,” says Waun Ki Hong, M.D., head of M. D. Anderson’s Division of Cancer Medicine and director of the BATTLE program.

All four treatment regimens have shown some activity against lung cancer and are taken in pill form. They are erlotinib (Tarceva®), vandetanib (Zactima™ ), sorafenib (Nexavar®), and a combination of erlotinib and bexarotene (Targretin®).

Tarceva and other new medications approved by the U.S. Food and Drug Administration in recent years to treat lung cancer have been shown to slightly increase overall patient survival. Biomarkers are needed to predict which patients are likely to benefit from the drugs.

“Tarceva won’t be any more effective in lung cancer than it already is, which is a little bit, unless we know who to give it to, at what dose and at what time,” says Roy Herbst, M.D., Ph.D., professor in the Department of Thoracic/Head and Neck Medical Oncology and BATTLE clinical trial coprincipal investigator.

As of mid-September, 75 patients were enrolled in BATTLE and assigned to one of the four clinical trials. The team expects to begin selective randomization this fall, with patients statistically nudged toward specific treatment arms. A total of 250 patients will be enrolled.

Research Nurse Christine Alden meets with potentially eligible patients to explain the trial and, in particular, to

review the need for multiple biopsies and the possible risks and discomforts of that procedure.

Interested patients return a week later to review the trial and give their informed consent to join. Next, they meet with interventional radiology to arrange for a biopsy the next day. Two weeks after the biopsy, patients have a return appointment, are randomized to one of the four treatment options and leave with the medication that day.

After eight weeks, another biopsy is performed, adds Ignacio Wistuba, M.D., associate professor in the Department of Pathology. Typically, “many biologic and biomarker studies are done only in specimens taken from the tumor before treatment. We think, however, it will be useful to do these studies in real-time so we can learn what’s happening after treatment because the tumor changes during therapy.”

Defeating lung cancer has never been easy, but it’s one battle investigators hope to win.

— Scott Merville

Edward Kim, M.D., and Research Nurse Christine Alden are helping patients battle lung cancer through an innovative clinical trial that targets specific biomarkers that fuel the disease.

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HOPE IS ON THE HORIZON Patients with Hodgkin’s lymphoma have more choices than ever

by Eileen A. Ellig

Anas Younes, M.D., wants no patient left behind.

He’s determined to give all patients with Hodgkin’s lymphoma a fighting chance.

A professor in M. D. Anderson’s Department of Lymphoma/Myeloma, Younes says it often can be difficult to get pharmaceutical companies interested in developing new drugs for a disease that affects only about 7,800 people each year and that already has a high survival rate, upwards of 85 percent at five years.

“But it’s not impossible,” he says. “You just have to do a lot of preclinical testing, provide a solid scientific rationale and show the true human impact of the disease.”

He and his team have been doing just that, working tirelessly in the laboratory to bring new therapies for Hodgkin’s lymphoma to the clinic.

While viewed as more curable than other cancers, “hidden from cure rates are the longterm side effects and development of second cancers,” he explains. “Not to mention that Hodgkin’s lymphoma strikes young people who have their whole lives ahead of them, only for it to be cut short because of the limited drugs available to treat the disease.”

Hodgkin’s lymphoma arises in the body’s lymphatic tissues, primarily involving the lymph nodes, which manufacture and store the all-important immune cells needed to help fight infection and disease. It also can affect other organs responsible for regulating the immune system and the production of blood cells, such as the spleen, bone marrow and thymus.

“Also hidden from view is the fact that nearly a third of patients will require additional therapy at some point,” says Younes, director of the department’s Clinical Investigational and Translational Research Program.

Thousands of these folks, he notes, have been hanging in there for years with little or no hope of a curative treatment after all current available therapies have been exhausted.

Kelly Stewart, a mother of three, was one of them.

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Anas Younes, M.D., says thousands of patients with Hodgkin’s lymphoma have been hanging in there for years with little or no hope of a curative treatment after undergoing all available therapies.

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FOURTH TIME IS A CHARM Extreme fatigue had plagued Stewart for years, but blood tests showed nothing abnormal.

Her doctor chalked it up to age, weight and chasing after her kids.

But all along, she knew this wasn’t a “normal tired,” plus a red rim resembling a necklace circled the bottom of her neck.

It took a move to northern California in 2002 and a friend’s prodding before the true reason behind her fatigue was uncovered. A routine X-ray revealed a lemon-sized tumor in her chest.

Stewart had Hodgkin’s lymphoma.

A concoction of four different chemotherapy drugs — the standard, frontline therapy for Hodgkin’s lymphoma — put her disease into remission, only to return four months later. She was then referred to an oncologist at Stanford University, a day’s drive from her home in Stockton.

There, Stewart underwent a transplant using her own stem cells to fight the disease — and for six months they did so valiantly before losing their strength. The next best thing to try, she was told, was a transplant using someone else’s stem cells. This meant finding a compatible donor.

“My brother and sister were fighting over who would donate,” Stewart laughs. “My brother’s cells matched so he won,” and so had she for the next year.

Then, the disease came back. “My doctor at Stanford said, ‘I can treat you, but I want you to be cured.

That’s my goal. I want you to go to M. D. Anderson and see what they have,’” Stewart recounts.

She wondered, could the fourth time be the charm?

So far, it appears to be.

ON BORROWED TIME Just two weeks later, Stewart boarded a plane headed to Houston, balancing hope in one hand and despair in the other.

Hope would prevail, as she soon discovered she had many options. “Dr. Younes was so positive, and there were so many things available to me that it really renewed my spirits,” Stewart says.

Several years ago that wouldn’t have been the case, Younes notes. “But today, we can offer patients like Kelly the opportunity to participate in several clinical trials that may give them more hope.”

Stewart was faced with a tough decision — which clinical trial to try. After careful consideration, she decided on a protocol testing an investigational agent that inhibits proteins supporting cancer cell survival. These proteins are called histone deacetylases, or HDACs for short.

To date, 18 different HDACs have been identified in human cells. Many of them have been linked to cancer cell growth and survival. Targeting HDACs with a new class of drugs called HDAC inhibitors is a hot strategy in cancer therapy, Younes says.

One HDAC inhibitor called vorinostat already is approved for treatment of a rare type of T cell lymphoma involving the skin. At least five other HDAC inhibitors are currently being tested in clinical trials in several cancers.

In laboratory studies, Younes and his team showed that HDAC inhibition may be a good strategy for treating Hodgkin’s lymphoma. They quickly designed a clinical trial to test the activity of a novel HDAC inhibitor called MGCD0103 in patients with relapsed Hodgkin’s lymphoma.

Younes says early results of this Phase II clinical trial have been very encouraging. At the annual meeting of the American Society of Clinical Oncology in June, Younes and his team reported that 40 percent of patients had major clinical responses to the experimental drug. Stewart was among them.

Like Stewart, these patients have tried virtually every treatment available, from chemotherapy to radiation to stem cell transplants, only to have those therapies ultimately fail them, Younes says.

Shortly after taking MGCD0103 orally three times a week, her tumors had shrunk considerably and then completely disappeared. She’s been in remission for more than a year.

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After several standard treatments failed, Kelly Stewart began taking an investigational agent

Now, Younes and his group plan to build on this success and combine MGCD0103 with other drugs to enhance its effectiveness. They’re also studying exactly how this agent works in Hodgkin’s lymphoma.

One theory is that MGCD0103 not only kills the cancer cells directly, but also may boost the immune cells to make them more competent in fighting the tumor cells.

“Hodgkin’s lymphoma is a unique and intriguing cancer because the primary cancer cells are less than one percent of the mass,” Younes says. “These so-called Reed-Sternberg cells originate from premature B cells that fail to develop into normal, mature functioning immune cells. The rest of the tumor mass is made up of reactive inflammatory cells, which is a normal immune response to any injury, infection or disease.”

With such an overwhelming advantage, “you would expect these immune cells to kill the tumor.

But they can’t,” he says. “What we find is they’re actually collaborating with the cancer cells, providing support by secreting factors that help the cancer to grow. It’s the ultimate immune betrayal.”

He believes MGCD0103 is influencing the reactive immune cells either by turning them into killer cells, or simply by getting rid of them.

Whatever the case, Stewart is happy it’s working.

that quickly eliminated her tumors.

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She has been through a lot over the years. “But I have come out on the other side really well. I’m hoping this drug will keep me in remission. If this nasty disease decides to come back, I know I still have lots of options.

I just live with it as best I can and hang on until they come up with something better.”

PLENTY MORE OPTIONS Younes believes the most rational treatment approach will be to combine these new active agents with current standard regimens, such as ABVD or ICE chemotherapy.

ABVD (Adriamycin®, bleomycin, vincristine and dacarbazine) is widely used in patients with newly diagnosed Hodgkin’s lymphoma, while ICE (ifosphomide, carboplatin and etoposide) is used in patients whose disease relapses after ABVD treatment.

Ultimately, Younes hopes that a combination of several new drugs will replace chemotherapy and provide a higher cure rate with reduced short- and long-term toxic effects.

Currently, there are several clinical trials evaluating novel agents, either singularly or in combination with standard therapy, for the treatment of Hodgkin’s lymphoma.

They include: s 0AIRING RITUXIMAB 2ITUXAN® WITH !"6$ CHEMOTHERAPY Already approved to treat non-Hodgkin’s lymphoma, rituximab is a monoclonal antibody that targets CD20, a molecule expressed on the outside of a cell. While the Hodgkin’s lymphoma Reed-Sternberg cells typically aren’t CD20 positive, about 20 percent of these cells will express it, says Michelle Fanale, M.D., assistant professor in M. D. Anderson’s Department of Lymphoma/Myeloma.

An earlier study showed that when used alone, rituximab decreased the number of CD20-positive Hodgkin’s lymphoma cells, Fanale says. It also wiped out the surrounding non-cancerous B cells, which nearly universally express CD20 and support the Reed-Sternberg cells’ growth.

These findings led to a Phase II clinical trial, testing whether rituximab plus ABVD chemotherapy could actually increase the number of patients who can be treated successfully.

“In the majority of patients, we’re seeing that it can, even for patients who have very advanced disease with lung, spleen and bone marrow involvement,” Fanale says. “They’re going into complete remission with this regimen. Now, several years out, most are still disease-free.”

WITHOUT A CAUSE

Michelle Fanale, M.D., and research nurse Gracy Zachariah are looking into the causes of Hodgkin’s lymphoma and investigating the potential of new drugs to treat the disease.

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Hodgkin’s lymphoma is a rebel without a cause.

There are suspects to be had, but no definitive outlaw willing to take the rap.

However, like in any good investigation, there are speculations and leads to follow.

The Epstein-Barr virus, which causes infectious mononucleosis, is suspect. Although not a clear-cut cause, patients who have had “mono” are more likely to develop Hodgkin’s lymphoma in the future.

“It’s thought that when people are exposed to EBV and subsequently develop mono, their B cells (a type of immune cell) are activated in response to the infection, which is a good thing,” says Michelle Fanale, M.D., assistant professor in the Department of Lymphoma/Myeloma. “But instead of returning to their normal state after fighting the infection, these B cells remain activated, possibly making them more susceptible to developing mutations that can eventually lead to Hodgkin’s lymphoma.”

The role EBV plays in Hodgkin’s lymphoma, however, is still questionable since many patients have no prior history of EBV infection, Fanale says. The current thinking is that while EBV might be associated with Hodgkin’s lymphoma development, there are many other factors involved. The presence of EBV in Hodgkin’s lymphoma cells may also predict outcome, she says, but this is still under investigation.

People with impaired immune systems, such as organ transplant recipients and those who have HIV and hepatitis, also have a higher likelihood of developing Hodgkin’s lymphoma.

It’s not evident, however, whether it’s the disease itself that makes them more vulnerable, or the immunosuppressive drugs they take to control their illness, Fanale says.

As one can see, Hodgkin’s lymphoma is still somewhat of a mystery — one Fanale and others want to unravel.

Often the first person a patient with Hodgkin’s lymphoma comes in contact with at M. D. Anderson is research nurse Amy Wedgwood. In her hands, she holds a list of clinical trials that may be their only hope for survival. Many of these patients have fallen in and out of remission one too many times, she says, and they think they have run out of options. But to their surprise, they learn there are now several new investigational agents available.

Wedgwood helps patients sort through the different protocols, determining which ones they qualify for. Once they’re officially enrolled in a study, she follows them throughout their treatment — checking vitals, going over lab results and PET scans, asking about side effects and answering a multitude of questions. She’s with them every step of the way.

While the best news Wedgwood and her patients can hear is that the drug is working, they know that it probably won’t cure everyone. “We hope it does,” she says. “But I always tell my patients that it’s trial and error. We’re learning as we go. And if one drug doesn’t work, we can try something else. Until they say ‘stop,’ we’re going to keep going.”

Fanale says a multi-center randomized Phase III clinical trial comparing rituximab plus ABVD to standard ABVD chemotherapy for patients with advanced-stage disease is the next step. If rituximab plus ABVD proves superior, “we hope to get this treatment approved as a new standard of care,” she says.

s #OMBINING BORTEZOMIB 6ELCADE® WITH )#% FOR PATIENTS WITH RELAPSED (ODGKIN S LYMPHOMA Bortezomib is used to treat multiple myeloma and mantle cell lymphoma. It works by blocking proteasomes (a cell’s equivalent to a garbage disposal), which are responsible for protein turnover. Inhibiting proteasomes leads to cancer cell death.

“Bortezomib plus ICE is producing early encouraging results that seem to be better than what we’re used to seeing with ICE alone,” says Fanale, who plans to confirm these results in a randomized study.

s %XAMINING THE EFFECTS OF 3'. AS A SINGLE AGENT SGN-35 is a monoclonal antibody similar to rituximab, except that it targets cancer cells expressing CD30 on their surface and has a toxin affixed to it. Hodgkin’s lymphoma cells express CD30 while normal cells don’t. Therefore, it’s believed that SGN-35 can potentially kill tumor cells while having little or no toxic effect on normal cells.

SGN-35 goes straight to the tumor cells, releases the toxin and then kills the cells. “It’s still early, but patients seem to be responding nicely,” Younes says.

Another anti-CD30 antibody, MDX-060, in combination with gemcitabine (Gemzar®) also is being examined in a Phase II clinical trial with promising responses thus far, Fanale says.

s %VALUATING THE EFFECTS OF !!' AS A SINGLE AGENT 17-AAG is a small molecule inhibitor of Heat Shock Protein 90, an essential protein required for maintaining the function of several survival proteins inside tumor cells, including those of Hodgkin’s lymphoma.

By inactivating this protein, investigators believe the function of the cells will be severely disrupted and as a result, they’ll eventually die. Laboratory experiments performed by Younes’ team showed that 17-AAG is effective in killing Hodgkin’s lymphoma cells. Based on these results, a Phase II clinical trial was initiated in patients with relapsed Hodgkin’s lymphoma.

So far, Younes says, “we’re seeing some positive responses in patients who have been heavily pretreated.”

Although it’s too early to know the long-term success of these studies, Younes feels they represent a major step forward in improving treatments for Hodgkin’s lymphoma after standing still for almost three decades.

“Not that long ago there wasn’t much hope for a lot of our patients,” he says, “but now there are several possibilities.”

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Hodgkin’s lymphoma has taken Marvin Hill Jr. down many unexpected paths.

But now in remission, he’s looking forward to taking long trips with his wife on his new Harley-Davidson motorcycle.

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“Dad, what’s wrong with your neck?�

That was the first thing Marvin Hill Jr.’s daughter said to him when she arrived home from college in the summer of 2000.

He knew then that the lump that had appeared on the side of his neck a little over a year before was something more than just the swollen gland his doctor originally suspected.

His daughter’s shock sent him straight back to the doctor. “Come to find out, I had Hodgkin’s lymphoma,� says Hill, who also learned he had some growths in his chest.

At a hospital close to his home in Katy, Texas, Hill underwent nine months of chemotherapy and a month of radiation.

For a time, these treatments held his disease in check. But as is the case for many patients with Hodgkin’s lymphoma, the disease recurred. “My 18-month tests showed it had come back,� he says.

He was told a stem cell transplant using his own cells would be his next best chance for beating the disease. He was referred to M. D. Anderson and underwent the transplant in 2003.

Hill enjoyed three, disease-free years, only for it to come back once again. He then asked his doctor, “What do I do next?�

Hill had two choices. One, to undergo another stem cell transplant, but this time using donor cells; or two, enroll in a clinical trial.

He opted for a clinical trial, and in October 2006, he began receiving an investigational agent that inhibits a protein responsible for keeping cancer cells alive. “It’s been keeping my cancer at bay for about a year,� he says, noting the side effects of the agent are minimal.

As protocol dictates, Hill can only stay on this trial for one year, at which time he has to stop taking this agent. He confides that he’s a bit apprehensive, but knows there are other investigational agents available if the need arises.

And, he says, “there’s always the stem cell transplant to try.

As it turns out, my daughter is a perfect, 10-for-10 match — the odds of that are less than a half percent. “I’m a lucky man.�

Surgery Spares Fertility

by Eileen A. Ellig

Denise Joost would like nothing more than to start a family.

That likelihood looked grim a few years ago when she was diagnosed with cervical cancer and told she would need a radical hysterectomy (removal of all the female reproductive organs) to treat the disease.

But as luck would have it, a clinical fellow rounding with her doctor that day mentioned he had heard of a procedure that could preserve her fertility.

Joost’s attention quickly turned to Charles Landen, M.D., now an assistant professor in M. D. Anderson’s Department of Gynecologic Oncology. “All of a sudden my focus shifted, and I wanted to know more.”

Landen was referring to a procedure called a radical trachelectomy, which is similar to a radical hysterectomy, except a woman’s uterus, or womb, is left intact.

Only about 500 such surgeries have been performed to date — most of them done outside the United States.

When Joost heard that M. D. Anderson was one of the few centers in the nation offering women this option, she welcomed the opportunity to discuss the procedure with Pedro Ramirez, M.D., associate professor in the Department of Gynecologic Oncology.

Ramirez has done more than 20 radical trachelectomies since 2005, after being trained by Daniel Dargent, a French surgeon who pioneered the procedure.

The possibility of maintaining her fertility while getting rid of the cancer seemed too good to be true, but was definitely something to consider, Joost says.

Newly engaged, she recalls telling her then fiancé, Chad, “If you don’t want to marry me because I might not be able to have children, I understand since that has always been part of our plan.”

His response to her was, “Your health is first and foremost, and I have no intention of spending the rest of my life with a baby and a memory of you.”

Buoyed by his love and support, Joost was ready to learn all she could about the radical trachelectomy.

After a radical surgical procedure to treat her cervical cancer, Denise Joost is now disease-free and ready to start a family with her husband, Chad.

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Pedro Ramirez, M.D., is offering women with cervical cancer a surgical option that not only treats their cancer, but also preserves their fertility.

A real page turner With three pages of typewritten notes in hand, Joost joked to Ramirez, “I hope you didn’t schedule the standard 10-minute doctor visit because you’re going to run behind all day.�

She and Chad had a lot of questions.

Ramirez wasn’t surprised. “He was very receptive,� Joost says, “and clear that patients before me had declined to have the surgery.�

Patients are told upfront that “this is a relatively novel approach and that we don’t know the true long-term side effects associated with it, although evidence suggests that the risk of recurrence and the overall survival is equivalent to having a radical hysterectomy,�

Ramirez says. “Therefore, outcome is not compromised.�

Joost learned that during the surgery, the cervix (the lower part of the uterus that connects to the vagina), the parametria (tissue located adjacent to the cervix), the area lymph nodes and the upper 2 centimeters of the vagina are removed. The uterus remains, however, and is then reattached to the vagina.

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Ramirez explains that since one of the primary functions of the cervix is to support a growing baby, a permanent suture, or cerclage, is placed where the cervix used to be “to assure there is no risk of losing the pregnancy.�

While a woman will most likely be able to conceive naturally, she’ll require a C-section at delivery because the tightly woven cerclage prevents a baby from passing through the vaginal canal, he says.

Women considering a radical trachelectomy often are concerned about the perceived likelihood of miscarrying.

While a common fear, Ramirez says that the risk of first and second trimester pregnancy loss is comparable to the general population.

Conception rates following surgery are favorable as well, he says. Of the women who have tried to conceive, approximately 50 percent have gotten pregnant and 73 percent of them carried their pregnancy to term.

Although these positive outcomes make the radical trachelectomy an attractive option, the surgery isn’t for everyone. “We’re very selective about who undergoes this procedure,�

Ramirez says. “It’s been shown that there is a higher risk of recurrence or need for postoperative radiation therapy if women don’t meet the specified criteria.�

To be considered for the surgery, women must have: s !N INTEREST IN FUTURE FERTILITY s ! DIAGNOSIS OF CERVICAL SQUAMOUS CELL CARCINOMA ADENOcarcinoma or adenosquamous carcinoma. s ! TUMOR LESS THAN CM s .O HISTORY OF INFERTILITY s .O EVIDENCE OF THE TUMOR EXTENDING INTO THE UPPER cervical canal and no detection of metastases, or spread, to the lymph nodes.

The procedure also isn’t without risk.

Some women may experience irregular bleeding, stop menstruating and become infertile as a result of the surgery. Vascular and nerve damage, and injuries to the bladder, urethra and rectum also have been associated with the surgery — although these complications are similar to those seen with a radical hysterectomy and other abdominal surgeries.

A bit of soul-searching For the thirty-something couple, information alone wasn’t enough to decide whether or not to have the radical trachelectomy. “We wanted to make sure we were doing it for the right reasons, which is that we wanted to have children, and that I really met all of the criteria,� Joost says.

The answer to both was “yes.�

They decided to go through with the surgery, knowing that Ramirez might have to do a radical hysterectomy after all if the cancer was more widespread than initially thought.

“We knew that could be necessary, so I gave him permission ahead of time to do what he needed to do,” Joost says.

“I was prepared for that. My only request was that Chad be the one to tell me what happened when I came to.”

Fortunately, everything went according to plan, and just four months after the surgery, Joost and Chad were married.

“I was relieved with the choice I made,” Joost says. “And even if we never have children, I’ll never regret having this surgery.”

Now two years out, Joost remains cancer-free and is trying to conceive.

Ramirez feels she has a good chance. “He’s waiting for me to call and tell him that I’m pregnant any minute now,” Joost says. “But no pressure!”

CERVICAL CANCER FACTS When detected early, cancer often can be managed and treated successfully.

This is especially true for cervical cancer, a disease that is expected to strike more than 11,000 women this year.

When discovered and treated in its early stages, the survival rate is 92 percent, according to the American Cancer Society.

Since its debut in the 1950s, the Pap smear has been the tried-andtrue way to screen for cervical cancer. Since then, it has significantly reduced the number of deaths related to the disease, says Pedro Ramirez, M.D., associate professor in M. D. Anderson’s Department of Gynecologic Oncology.

The Pap test can identify abnormal cells in the cervix that, if left unchecked, could lead to cancer, including those changes brought on by the human papillomavirus. HPV is a sexually transmitted disease.

Most often cervical cancer can be linked to HPV infection. In particular, two strains of the virus — HPV 16 and 18 — are highly associated with the disease, accounting for 70 percent of all cases.

These, and two other types, which cause 90 percent of genital warts, are the target of a new vaccine that prevents the virus from taking root and causing cancer.

Fallopian tube Fimbria

Approved by the U.S. Food and Drug Administration in 2006, Gardasil® is recommended for females ages 9 to 26 and is best admin-

Uterus

istered before one becomes sexually active or is exposed to HPV, Ramirez says.

While women of all ages can develop cervical cancer at any time,

Cervix

Ovary

Vagina

Broad ligament

Ramirez notes that those who have had sexual intercourse at an early age, who have multiple sexual partners and who smoke are more at risk.

It’s important, he stresses, that women continue to get routine Pap

Illustration by Kathleen Wagner

smears since the test can pick up early disease, even before a woman

During a radical trachelectomy, the cervix, the tissue and

experiences any symptoms. Typically, there are no early warning signs

area lymph nodes surrounding the cervix, and the upper 2

indicating that something may be amiss.

centimeters of the vagina are removed. The uterus remains, however, and is then reattached to the vagina.

If a woman, however, has any abnormal bleeding or discharge, bleeding after intercourse and/or pain, she should consult her physician.

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30 Years of Finding Answers in the Lost Pines

Virginia Harris Cockrell Cancer Research Center scientists unravel origins of cancer

by Scott Merville

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IM.mmersed in the environmental awakening of the 1960s and 1970s, D. Anderson’s first president, R. Lee Clark, M.D., pursued a dynamic vision to build a research park in the Lost Pines region of Central Texas, modeling it after North Carolina’s Research Triangle Park.

In an arc from San Antonio to Austin to Houston to Galveston, Texas research institutions would build a world-class presence in environmental science and ecology, studying the effects of environmental factors on cancer and other major diseases.

Clark worked with the Texas Department of Parks and Wildlife, the City of Smithville, Bastrop County and the Texas Legislature to transfer 717 acres of land in Buescher State Park, 40 miles southeast of Austin, to The University of Texas to house the research park.

While other institutions bowed out of the plan in those less collaborative times, M. D. Anderson stayed and thrived. Since 1977, M. D. Anderson’s Science Park-Research Division at the Virginia Harris Cockrell Cancer Research Center in Smithville, Texas, has earned international recognition from its unique rural location, camped scientifically at the tangled crossroads where the varied pathways that lead to cancer meet.

Scientists at the Cockrell Cancer Research Center have made significant contributions over the past 30 years, including establishing the first direct link between a chemical carcinogen in tobacco smoke and human lung cancer, discovering a cellular receptor that plays a crucial role in regulating the immune system and identifying a tumor-suppressor gene involved in melanoma susceptibility.

The five-year, $8.3 million renewal grant from the National Institute for Environmental Health Sciences came as the Cockrell Cancer Research Center celebrated three decades of detecting the origins of cancer at its labs in Central Texas. The grant continues funding of the 10-year-old Center for Research on Environmental Disease, one of only 23 centers in the nation exploring environmental causes of disease.

The word “environmental” often conjures up images of air and water pollution, and toxic chemicals in workplaces and neighborhoods. To those factors, scientists also add natural carcinogens, such as ultraviolet light from the sun and behavioral factors, such as diet and use of tobacco and alcohol. Other conditions, such as obesity, are separate risk factors for cancer, heart disease and diabetes.

“This center is very broad in its approach,” DiGiovanni says. “We study everything from the molecular mechanisms of how environmental agents cause toxicity and induce cancer to how diet affects our responses to environmental exposures to the interactions between genes and these external factors.”

Expanding scope Understanding carcinogenesis — the birth of cancer cells — is the facility’s core expertise, but in its 30th year, a major grant renewal expands the scope of its research to other diseases and cultivates institutional collaboration in the spirit of Clark’s vision.

“It takes a broad multidisciplinary approach to understand how genes interact with environmental factors to cause cancer,” according to John DiGiovanni, Ph.D., director of the Cockrell Cancer Research Center and chair of M. D. Anderson’s Department of Carcinogenesis. “One long-term goal of our research is to identify genetic characteristics that pose a high risk for development of cancer due to environmental exposures. Then, we want to offset that increased risk by, for example, altering a person’s diet or developing novel chemopreventive strategies.”

Xuetong Shen, Ph.D., and his colleagues found that two molecular pathways work together to protect cells against DNA damage and may provide new targets for attacking cancer.

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center with The University of Texas at Austin that conducts basic toxicology research.

While the grant renewal expands translational research and encompasses new categories of disease, scientists at the Cockrell Cancer Research Center continue to make important discoveries.

Two meaningful examples come from Assistant Professor Yinling Hu, Ph.D., and Associate Professor Xuetong “Snow” Shen, Ph.D., who recently published their findings in major journals.

Silencing a cancer defense

Yinling Hu, Ph.D., and her team discovered that the absence or weak expression of a specific protein found in skin cancer results in genetic instability and disease development.

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A new feature of the center is a greater focus on translational research, he adds. Translational research is the bridge between basic science research that discovers fundamental molecular aspects of disease and clinical research that carefully tests new prevention and therapeutic strategies in patients.

Most of the center’s work is in preclinical translational research, the testing of lab findings in animal models. Collaboration with M. D. Anderson’s Department of Epidemiology and a new connection to The University of Texas School of Public Health at Houston provide ties to population research.

Clinical associations include participation in three M. D. Anderson Specialized Programs of Research Excellence grants in prostate, gynecologic, and head and neck cancers. SPORE programs are a National Cancer Institute initiative to encourage more efficient translation of laboratory findings to the clinic.

The UT School of Public Health adds expertise in monitoring an individual’s personal exposure to airborne toxins and carcinogens. “This will bring a new research focus on air pollution and human health. Our colleagues focus on asthma and cardiovascular disease, so this will clearly broaden the scope of environmental diseases under study at the center,” DiGiovanni says.

The grant also includes the Center for Molecular and Cellular Toxicology, a joint interdisciplinary

Cells divide to multiply. As a cell splits into two identical versions of its former self, the process is halted temporarily by checkpoint genes, which allow the dividing cell to be analyzed for genetic damage.

Normally, genetic errors found at the checkpoints are either repaired by specialized cellular machinery, or the cell is forced to kill itself to prevent the damage from spreading.

Hu found that a protein largely absent in one type of skin cancer normally protects an important checkpoint gene from being chemically turned off.

Restoring the expression of the missing protein, called IKK, also restored the checkpoint gene, which had been silenced by a chemical process known as methylation. Methyl groups, consisting of a carbon atom surrounded by three hydrogen atoms, attach to specific locations on a gene and prevent the gene from expressing its protein.

“DNA methylation is largely responsible for shutting down the checkpoint gene expression in human cancer cells,” Hu explains. “Our finding opens a new avenue for identifying new therapeutic targets for battling cancer. Those targets may be used to prevent silencing of the gene in cancer cells and allow us to eliminate those cells.”

Published in the journal Molecular Cell, the paper

by Hu, lead author Feng Zhu, Ph.D., and colleagues focused on aggressive squamous cell carcinomas.

However, the checkpoint gene is silenced in a variety of other human epithelial cancers. Epithelial cells make up the outer layers of skin and the inner linings of many organs, including the lungs and the gastrointestinal, reproductive and urinary tracts.

It’s all in the packaging It’s easy to think of genes neatly lined up on our 23 chromosomes, carefully spelled out in various combinations of the four bases that are the building blocks of DNA. Not quite, Shen says.

DNA is tightly intertwined with proteins known as histones and assembled in histone/DNA units called nucleosomes along the connecting length of a string of DNA. “This structure is often referred to as beads on a string,” he says, and is collectively known as chromatin.

So it’s not just about genes, it’s also about how they are, in effect, packaged.

“Chromatin creates barriers to DNA against anything that wants access to DNA,” he explains. “Chromatin remodeling shuffles the nucleosomes around to create access to DNA. This moving and sliding of the ‘beads on the string’ is accomplished by large protein complexes.”

In the journal Cell, Shen and colleagues describe how a chromatin remodeling complex he discovered connects with a damage control pathway to contain DNA wreckage.

When genetic damage occurs, a group of signaling proteins regulate the checkpoint and repair pathways by attaching phosphate groups (chemical compounds) to other proteins involved in damage control.

“We found that one of the proteins that gets the phosphate groups was a subunit of a chromatin remodeling complex, and apparently the cell uses this event to regulate DNA damage response,” Shen says. “This connection between a signaling pathway crucial to DNA damage control and a chromatin remodeling pathway opens an entirely new category of targets for potentially attacking cancer.”

Discoveries to be continued The molecular story of cancer’s origins has progressed from genetic mutation to genetic damage to specific checkpoint and repair pathways to the nuances of chromatin.

As the tale grows more complicated, Smithville scientists dig ever deeper into the details.

Along the way, they know they can count on the surrounding community.

“Local support has always been a wonderful aspect of the Cockrell Cancer Research Center,” DiGiovanni notes.

“Friends of the Science Park provide moral support and financial help for us. We greatly appreciate their efforts.”

About $45,000 in proceeds from the anniversary celebration and related events will fund carcinogenesis research.

Science in the Community Robin Fuchs-Young, Ph.D., and the staff of the Community Outreach and Education Program want everyone to appreciate the benefits of biomedical research and to learn how to prevent environmental disease, especially cancer.

A grant from the prestigious Howard Hughes Medical Institute may help them do that sooner than later. The five-year, $750,000 award funds a comprehensive project to enhance science and health education in Smithville, Texas, schools and to promote community interest in science and biomedical research.

“Our future scientists are in the classroom right now. It’s vital that we expose them to the importance of science and the many opportunities for scientific and research careers,” says Fuchs-Young, director of COEP at M. D. Anderson’s Science Park-Research Division at the Virginia Harris Cockrell Cancer Research Center in Smithville.

Fuchs-Young and the COEP have a tradition of educational outreach that underpins the Howard Hughes grant, the first awarded to M. D. Anderson.

The Howard Hughes project, known as CENTIPEDe, which stands for Community Education Networks to Integrate Prevention of Environmental Disease, will tailor health and science educational programs to the specific needs of Smithville schools and the community.

CENTIPEDe will provide increased access to science for students through onsite field experiences, hands-on classroom activities, research internships and mentoring opportunities.

For elementary, junior high and high school teachers, there will be workshops and professional development sessions with center faculty and staff, as well as From her lab in Smithville, Texas, Robin assistance with lesson plans, summer felFuchs-Young, Ph.D., is bringing science lowships and activities that provide a “real and biomedical research to area schools world” context. and the community.

Graduate and post-doctoral trainees who have chosen science for their life’s work will have increased opportunities for career development, including teaching and mentoring students.

CENTIPEDe also will support community programs to enhance scientific literacy and acquaint parents and other Smithville residents with research discoveries and important health information.

Research by national education organizations shows that rural communities have special challenges with science education, according to Fuchs-Young. Students in a rural setting often have limited access to educational resources at school, home and within the community.

The project is a collaborative effort between the Cockrell Cancer Research Center and the Smithville community to develop educational resources and opportunities and to provide these programs to rural communities and educators at the local, state and national level.

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Editor’s Note: Studying symptom-related data to improve survivors’ daily lives is the central focus of M. D. Anderson’s Department of Symptom Research. This is the second in a series of articles that details the steps being taken to collect solid, scientific evidence that can be used to design interventions to relieve the symptom burden caused by cancer and its treatments.

Using a computer- and telephone-based assessment system, lung cancer patients can use a telephone’s keypad to report post-surgical side effects, rating the severity of symptoms on a scale from 0-10.

MEASURING THE IMMEASURABLE Cancer patients enter treatment with endless questions. The first one is typically, “Will the treatment be successful?” But quickly on its heels is another, “What will the side effects be?”

Given the challenges oncologists face working towards answering the first question, it’s understandable that the second one has received little attention until now. What has been lacking are tools to help health care providers understand and measure the symptom burden patients experience during and after treatment.

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by Sandi Stromberg Charles Cleeland, Ph.D., chair of M. D. Anderson’s Department of Symptom Research, and his team are working to address that need. While it’s a long journey from scientifically identifying symptom distress to discovering the biologic mechanisms that cause these symptoms and creating interventions, they’re taking the first steps.

One of several collaborations they’ve undertaken across the institution is with physicians, advanced practice nurses and mid-level providers treating patients with non-small cell lung cancer. Currently, there are three studies working toward a continuum of symptom management for patients with non-small cell lung cancer from stage I to stage IV. TECHNOLOGY ANSWERS THE CALL: EARLY STAGE DISEASE Ara Vaporciyan, M.D., associate professor in the Department of Thoracic and Cardiovascular Surgery, helps his patients understand the side effects of their surgery. But much of what he’s been able to tell them until now was anecdotal, not evidence-based. The ongoing challenge he and his colleagues face is gathering symptom-related data in real time.

Now, working with Xin Shelley Wang, M.D., associate professor in the Department of Symptom Research, he and fellow surgeon Assistant Professor Wayne Hofstetter, M.D., are testing the effectiveness of an interactive voice response system on postoperative symptom control. Wang is the study’s principal investigator.

The IVRS is a computer- and telephone-based assessment system that allows patients to report distress, sleep disturbance, shortness of breath, constipation and pain — side effects for which they can offer interventions.

All patients enrolled in this ongoing randomized study receive a weekly phone call from the IVRS. In turn, they use their telephone keypads to rate on a 0-10 scale — with 0 meaning not affected, 10 as bad as you can imagine — and record symptoms as they occur.

If any of the targeted symptoms exceeds the threshold value chosen by the investigators, one of two things happens: s &OR THE CONTROL GROUP THE INFORMATION IS RECORDED AND ARCHIVED FOR STUDY AT A later date. s &OR MEMBERS OF THE STUDY GROUP INFORMATION ABOUT SYMPTOMS IS FORWARDED TO THE heath care team to review and potentially act upon.

Clinical interventions are handled by Sherry Wright and Madonna Berry, advanced practice nurses in the Department of Thoracic and Cardiovascular Surgery. They are working with Beth Johnson, a research nurse supervisor in the Department of Symptom Control.

“This study provides us with data that allows me to have a greater understanding of what my patients go through so I can better prepare future patients for surgery. It also allows us to determine if the IVRS could be helpful in symptom management during this acute postoperative phase,” Vaporciyan says. “We’ve learned that pain is highest after surgery and then decreases.

But after a month, it increases again, only to drift back to baseline after four to five months.

“Simply knowing that the pain will most likely increase and conveying this to the patient helps us alert them to move a little slower and to avoid unnecessary pain.”

A GOOD STARTING POINT: STAGE II-IIIB For most patients with locally advanced unresectable non-small cell lung cancer, standard care consists of concurrent chemoradiation, which has both acute physical and non-specific symptoms that contribute to patients’ general distress.

To better understand this burden, 64 patients being treated in the Department of Radiation Oncology were recruited to a study that used the IVRS and the M. D. Anderson Symptom Inventory, MDASI-Lung questionnaire. Each patient was contacted weekly during the 12-week treatment regimen and asked to report the severity and impact of cancer-related symptoms.

This longitudinal study, published in the Journal of Clinical Oncology in September 2006, also allowed researchers to document a symptom cluster that has the strongest impact on this patient population’s daily functioning, yet one whose effects are often ignored in patient care: fatigue, lack of appetite, drowsiness, sleep disturbance, dry mouth and distress.

“This study is very important in helping us educate patients,” says Zhongxing Liao, M.D., associate professor in the Department of Radiation Oncology. “Before a patient starts treatment, we can go over symptoms associated with the treatment. Patients appreciate that. We used to get complaints like, ‘Nobody told me this was going to happen,’ or ‘I didn’t know this was going to be so bad.’

“This tool helps us explain to patients what’s going to happen at each stage of treatment and the time frame for recovery.”

Liao says they also found their assumption that patients would feel better toward the end of treatment as the body started to heal was not true. “We learned that symptoms last two to three weeks after treatment. In fact, they probably get worse during the first and second week after completion of chemoradiation.”

Radiation oncologist Zhongxing Liao, M.D., uses the MDASI-Lung questionnaire to better understand the symptoms lung cancer patients experience and to help them know what to expect during and after treatment.

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Advanced Practice Nurse Kay Herndon (left) works with Charles Lu, M.D., and Research Nurse Beth Johnson to enroll lung cancer patients in studies using an interactive voice response system and a lung symptom questionnaire.

FATIGUE AS A PREDICTOR: ADVANCED LUNG CANCER One of the most important findings to date was presented at the 2007 meeting of the American Society of Clinical Oncology. In an ongoing longitudinal study of patients with advanced-stage nonsmall cell lung cancer, researchers used the IVRS and the MDASI-Lung questionnaire to collect data from patients who were about to begin chemotherapy. They then followed them for 18 weeks over the six-cycle treatment regimen.

What they found was that the level of fatigue patients reported at the beginning of treatment with platinum-based chemotherapy predicted survival. The higher the fatigue, the less chance they would continue the therapy and the shorter their life span.

“We knew this intuitively,” says Charles Lu, M.D., associate professor in the Department of Thoracic/ Head and Neck Medical Oncology. “So you might ask, why study this? The difference is that we’ve been able to measure and quantify something that’s very hard to measure and quantify. And we’re doing it before a patient starts treatment. This data hasn’t existed. No one has treated lung cancer patients with chemotherapy and then contacted them every week to get a thorough inventory of their symptoms. It’s something that takes time and effort.”

Lu also has found that when patients discover their commitment in the study is not burdensome, it’s only a phone call and takes less than five minutes, they’re quite willing to participate.

As this study moves into its second funding phase, Cleeland also is involved with Houston’s large underserved population through the Harris County Hospital District and Lyndon Baines Johnson General Hospital. He and his colleagues are using the MDASI-Lung questionnaire and the IVRS to see if what they’ve learned in a predominantly white, non-Hispanic group has relevancy among different ethnicities.

“Our entire department is behind this,” Lu concludes. “We feel it’s a very novel and fruitful avenue of research and one sorely lacking until now.”

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In the spring issue, the series continues with a look at the symptom burden of patients with head and neck cancers.

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by Mary Jane Schier

J

anet M. Bruner, M.D., was a new pharmacist planning to conduct drug research when a mentor suggested she study medicine. Following that advice would propel her to a productive career as a neuropathologist at M. D. Anderson.

While taking a medical school course in pathology, Bruner got hooked and remembers, “I was fascinated to learn about the disease processes and how crucial pathologists are to the medical care team, starting with making definitive diagnoses for hundreds of diseases and continuing through to determine the causes of death. I knew right away this field was for me.�

Bruner was encouraged by several pathology instructors at the Medical College of Ohio at Toledo. She considered specializing in forensic pathology, but then a neuropathologist inspired her to follow in his footsteps. “Studying the intricacies and special language of the human brain introduced me to a whole new world. The brain is distinctly different from all other organs because it’s the center of our intelligence, memory and emotions, and it controls movement and speech. The more I understood the brain’s unique anatomy, the more intrigued I was,� Bruner explains.

Now, three decades after first examining pathology slides with brain tumor tissue, Bruner is professor and chair of the Department of Pathology and deputy head of the Division of Pathology and Laboratory Medicine at M. D. Anderson. She also holds a joint appointment in the Department of NeuroOncology. “M. D. Anderson has afforded me with more opportunities than I ever could have dreamed,� she says.

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Bruner received a bachelor’s degree in pharmacy and a master’s in pharmaceutical sciences from the University of Toledo before earning her medical degree at the Medical College of Ohio at Toledo. After completing a residency in anatomic and clinical pathology and being chosen chief resident at the Medical College of Ohio Hospital, she came to Houston in 1982 for a two-year fellowship in neuropathology at Baylor College of Medicine. “I always planned to return to Ohio,� Bruner recalls, “but during my fellowship I had the good fortune to spend time at M. D. Anderson working with an expert in electron microscopy and to meet neurologists developing a neuro-oncology program.�

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Operating room nurse requests rapid diagnosis of a patient’s tissue sample.

Clinical Histology Technician Davis Parambil checks on tissue being frozen quickly to minus 50 degrees.

Pathology fellow slices the frozen tissue to place on slides.

Histology Laboratory Assistant Angela Calhoun helps Pathology Fellow Christopher Vinh Nguyen, M.D., prepare and stain slides.

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Janet M. Bruner, M.D.

Upon finishing the fellowship, she was invited to join M. D. Anderson, where for awhile she was the only neuropathologist. Bruner thrived as the Departments of Neuro-Oncology and Neurosurgery expanded to offer innovative therapies for an increasing number of patients with brain and spinal cord tumors. She was chief of the Section of Neuropathology and directed the Diagnostic Hybridization Laboratory for 14 years, during which she began conducting laboratory research and taking leadership courses that prepared her for management positions.

In 1998, Bruner became the first woman faculty member to chair a clinical department, the initial holder of the Ferenc and Phyllis Gyorkey Chair in Pathology and the deputy head of the new Division of Pathology and Laboratory Medicine. She immediately polled the pathology faculty about organizing into subspecialties that would align them with the diseasesite centers and clinical research initiatives while strengthening the department’s educational programs.

Since then, the department has expanded in parallel with the institution’s growth in patients served.

“We’ve nearly doubled our faculty — from 29 in late 1998 to 56 today — and are divided into 11 subspecialties that allow us to interact more effectively with the surgical and medical specialists and keep up with their patient increases,” Bruner notes.

This year, the pathology faculty and support staff will provide diagnostic and staging evaluations on more than 60,000 surgical cases. At least one-half of that total will be for outside consultations (see sidebar, page 23).

Pathology Professor Kenneth Aldape, M.D., evaluates slides containing normal and cancer cells.

Subspecialists include 11 devoted to breast pathology, seven for gastrointestinal and liver tumors, six gynecologic pathologists and six for soft tissue tumors. Others provide pathology services for surgeons who remove genitourinary, head and neck, skin, brain and spinal cord, orthopedic and thoracic (lung and endocrine) tumors.

In addition, there are 12 cytopathologists who annually process 20,000 cases, analyzing tissue removed during fine needle aspiration biopsies, cells scraped from the cervix for Pap smears and other cells extracted from fluids that shed into body cavities.

The department offers autopsy services and operates laboratories that provide highly specialized tissue analyses to support clinical and research programs.

Pathology faculty work closely with colleagues in the Department of Hematopatholgy, which is responsible for evaluating bone marrow and lymph node specimens for clinicians who treat patients with leukemia, lymphoma and myeloma and who provide stem cell transplantation and cellular therapy.

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Memories of wonderful mentors have motivated Bruner to set high standards for training the next generation of pathologists.

“I’m proud of our pathology fellowship program, which averages 25 clinical fellows a year and is the largest in the United States. Because M. D. Anderson sees every type and stage of cancer, we offer fellows the broadest training possible. Some will take part in more complex or rare evaluations in a few months

Pathology Chair Janet M. Bruner, M.D., tells a neurosurgeon that the frozen section analysis shows his patient’s brain tumor can be removed.

been considered inoperable can be removed or is not an aggressive cancer.

Other tissue samples not needing a rapid diagnosis are processed through the frozen section laboratory, placed in color-coded plastic holders and sent to the routine histology laboratory to be cut into sections for slides that are stained before going to pathologists and fellows for final analysis.

Written pathology reports are sent to the surgeons within three days to share with their patients.

An 11-headed teaching microscope helps Pathologist Hafeez Diwan, M.D., Ph.D., (center) discuss slides with pathology fellows before sending diagnostic reports to clinicians.

than many community pathologists will see over a whole career,” Bruner says.

The fellows rotate through all areas of pathology and often hear Bruner remind them that “behind every single pathology slide is a patient depending on our expertise.”

One location where that phrase is most relevant is the frozen section laboratory on the fifth floor of Alkek Hospital. Surgeons in nearby operating rooms can count on rapid diagnoses of their patients’ biopsy tissue within 20 minutes.

Bruner explains the process for analyzing brain tumor tissue, which often measures only 1 millimeter in size. An operating room nurse brings a tissue sample to the frozen section laboratory window and rings a bell. Within seconds, the tissue is placed in a custom-fabricated machine made at M. D. Anderson to freeze the tissue quickly to minus 50 degrees. The frozen tissue is sliced, placed on slides, stained so normal and malignant cells can be evaluated, and examined under the microscope

by Bruner or another neuropathologist.

Any pathologist performing a rapid diagnosis will ask a fellow to view the slides while they discuss the findings, then the pathologist calls the surgeon on a special intercom to report the frozen section results. The best scenario for Bruner occurs when she can tell the neurosurgeon the tumor that had

Seeking a Second Opinion Thousands of cancer patients who never come to M. D. Anderson are indebted to the institution’s pathology expertise provided through second opinions.

“Our outside consultation service prepares approximately 30,000 second

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opinions annually to help physicians

“You always hear on TV or read in the paper about some celebrity waiting for the results after being operated on for cancer, yet most people don’t know those results depend on pathologists,” Bruner says with a wry smile.

elsewhere classify all types of cancer

Speaking of results, she says new patients who have had biopsies before coming to M. D. Anderson are asked to send ahead or bring pathology slides with them.

“We provide an extensive review of their slides and actually change the diagnosis for at least 10 percent of patients, either finding they don’t have a malignancy or they may have a less severe disease that can be treated,” Bruner says.

Bruner’s research includes tissue-based and molecular analyses of human brain tumors to discover molecular markers that will better define prognosis and predict survival for patients. She contributes to the interdisciplinary Brain Tumor Program Laboratory that identifies and prepares primary brain tumor tissue for research studies.

Among accolades, Bruner is included in several “best doctor” lists, is a past president of the Houston Society of Clinical Pathologists and has received distinguished alumnus awards from her medical school, college and high school. She and her husband, Charles, a retired pharmacist, share their Houston home with their fifth miniature schnauzer, whose registered name is Bruners’ Live Long and Prosper, but who answers to Louis.

“We start our mornings walking an hour with Louis, who provides positive reinforcement that we expect to have a good day,” Bruner says.

and choose the most effective treatments for their patients,” explains Janet M. Bruner, M.D., chair of the Department of Pathology.

Tissue samples on glass slides sent by overnight delivery are processed quickly and written reports are returned to the requesting physicians, usually in two to four days. The basic evaluation fee of $250 sometimes is covered by patients’ insurance or can be paid by the patients or their primary physicians.

Besides having pathologists in 11 cancer subspecialties, Bruner says additional diagnostic tests are available through specialized laboratories for image analysis, electron microscopy, diagnostic hybridization and immunocytochemistry.

In recent months, second opinions on pathology specimens have been sought by physicians for patients as far away as China, India and Iran.

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Moving Forward: Robert Dorsey Jr.

by Sandi Stromberg

Robert Dorsey Jr.

A process technician in the chemical industry, Robert Dorsey Jr. is given to quoting the French philosopher René Descartes and the English philosopher and economist David Hume.

Little wonder that when he graduated from the University of Houston-Clear Lake at the age of 52, he was named the 2002 Outstanding Undergraduate Student in Humanities.

He had planned to finish his degree earlier, but a diagnosis of Hodgkin’s lymphoma in 1995 and subsequent treatments slowed him down.

“Then, I started to lose my hair,” he laughs. “So, I decided to shave it all off and get a new look. I made it a happy walk.”

He also found myriad ways to keep quality in his life.

Using a recipe book, he made a variety of juices. He watched his diet, visited M. D. Anderson’s chapel, used onsite computers to learn as much as possible about his cancer, enjoyed the volunteers who played the piano in the lobby and joined his church choir.

“I also kept a daily journal of what was going on,” he says. “If something was happening I wasn’t sure about, I

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wrote it down so I had a record and could give feedback to the doctor.”

Dorsey continues to inspire his colleagues, urging them to get regular prostate examinations and colonoscopies. “My experience is something I don’t mind talking about. I always tell people that we’re blessed to have the best treatment center in our backyard when so many others have to come from so far.”

Fortunately, Dorsey’s cancer has been in remission since the mid-1990s, so he continues his 12-hour-on, 12-hour-off shift work, providing steam, process water and air for the NOVA Chemical plant in Bayport, Texas. He’s also a member of the plant’s rescue team and fire brigade.

“I just try to make sure I’m well-rested, eat decently and retain a certain amount of exercise,” he says.

This is a formula that seems to work for this processing philosopher.

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James Richard Huffines, Austin Chair

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John W. Barnhill, Jr., Brenham Judith L. Craven, M.D., Houston

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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 Office of Public Affairs -Unit 229, M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, 713-792-0658. E-mail: eellig@mdanderson.org.

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