Logan Spector is not a medical doctor, but he does have the opportunity to talk with families as part of his research work. In his experience, the first question asked by parents whose children have been diagnosed with cancer is: What’s going to happen to my child? The second question is: Why did this happen to my child? Epidemiologists like Dr. Spector are “here to investigate the why.”

Back in 2004, a small seed grant from Rein in Sarcoma helped Dr. Spector support a successful application for funding from the National Institutes of Health. NIH funding allows him to study the connection between osteosarcoma and certain genes. The entire field of genetic epidemiology has been revolutionized, with the possibilities changing dramatically in just the last decade. In other work, Dr. Spector uses new technology that could increase the chances of finding key connections between troublesome genes and aggressive cancers. The University of Minnesota, where Dr. Spector is an Associate Professor, is “a great place to study pediatric cancer.” It’s not quite the life led by Colonel Sam Daniels, but it suits him well.

A Beginning

At The College of William and Mary, Logan Spector studied biology. For his life, Dr. Spector sought a field where he could use this science without being tied to a lab. Epidemiology offers these possibilities. For a time, Dr. Spector was intrigued by Colonel Sam Daniels, the character played by Dustin Hoffman in the 1995 movie “Outbreak.” But then he discovered that Hoffman played a virologist, not an epidemiologist. What’s the difference? Virologists chase down viruses, sometimes deadly and always contagious. Not the best fit for a man who wanted to have a family one day. And not the study of people, which is what Dr. Spector found really interesting.

Epidemiology is the study of people. Groups of people, put into categories and then compared. Researchers look for the factors that make a difference. Is one group more likely to suffer disease than another? If scientists can find out why, then we may be able to prevent the harm. Even when this is not possible, it can be helpful to know our chances. And in cancer research, naming the targets can lead to break-throughs in treatment.

When I think about break-throughs in treatment, I tend to think of fancy new drugs. But here is a more stealth example, at least for those of us who don’t do this for a living: Scientists have discovered that children who have one particular version of a certain gene will face a great risk of getting sick from one of the main treatments used for acute lymphocytic leukemia. Because they know this, doctors now can test their patients to look for this gene. If the children have the version that places them at risk, doctors can lower the dose of the drug, and lower the chance the kids will get sick. Steps like these can lead to real differences in many lives.

Making this difference seems to call Dr. Spector, who received his PhD in Epidemiology from Emory University in 2002. He began with an intention to work with infectious disease. His dissertation led him to childhood leukemia, however, and he has worked with pediatric cancers ever since.

Calling for Investigation

Like many of his colleagues, Dr. Spector is drawn to challenging and important questions. After he arrived at the University of Minnesota, one of his first assignments was to write a book chapter on childhood cancer. So he dove into the literature. There he discovered osteosarcoma and Ewing’s sarcoma, two cancers that were “ripe for study.”
In osteosarcoma, there was “this very strong clue” that the cancer “mirrors puberty almost exactly.” Girls peak earlier than boys, both in their age for getting the cancer and in their age for puberty. Boys peak later, and their peak is higher than girls. Their pubertal growth spurt is longer and more intense – they get taller and bigger, on average, than girls – and they also have higher chances of getting osteosarcoma.

Ewing’s sarcoma arises almost exclusively in children of European descent. It also is strongly associated with hernia. This means that children who have certain kinds of hernias are more likely to get the cancer than would be expected just by chance. And don’t think, here, about those hernias your friends may get from lifting too much weight. The hernias that are linked with Ewing’s sarcoma are inherent weaknesses in tissue structure, affecting for example the umbilical cord, the diaphragm or the intestines. People are born with these weaknesses. This suggests a possibility that Ewing’s sarcoma could be caused by things that happen before children are born.

Basically, there was this “grab bag of things that did not fit well together,” which, to Dr. Spector, was “collectively calling for investigation.” And so he has investigated, with fine mentoring from Dr. Julie Ross, who brought him to the University through a research training grant and who continues to serve as his mentor today.

Revolutionary Advances

If you think of the human genome as a book, the Human Genome Project found the first letter of every sentence, and the period at the end of each sentence. Next, scientists began to fill in every seventh letter of each sentence. Now, scientists are in the process of discovering every letter in every sentence. Dramatic changes have occurred in this field, even since Dr. Spector began his work in 2002.

Several years ago, when scientists wanted to look for certain genetic changes that might be important for cancer, they needed to decide up front. Using the clues they could find, researchers would name the genes they were going to study. The problem with this method is that we people have about 30,000 genes. The ways they combine together, and the things that can go wrong, are almost too many to count. So the chances of hitting on just the right connection, between bad genes and bad cancers, were not great. The studies based on these predictions ended up having a fairly poor track record, as scientists learned that “we don’t know as much as we think about what might be relevant.”

Enter the Genome Wide Association Study, which now allows scientists to “put a genome on a chip and get back a million base pairs.” I’m not really very sure what this means. But I do understand that what it promises is a much better ability to compare information across people and cancers, and to figure out what really matters. Dr. Spector’s current work includes this kind of research for both osteosarcoma and Ewing’s sarcoma.

“Those of us who’ve been paying attention,” notes Dr. Spector, have heard a lot of hype for the last 10 years about the benefits of personalized medicine. The benefits “have not materialized as fast as we’d like. But it will happen.” Particularly for childhood cancers, the benefits will come.

We await this future. And are glad that bright young minds continue to engage the clues.

By Christin Garcia

Dr. Subramanian has been researching sarcomas since 2003. Although only few funding resources are available for sarcoma research compared to other cancers, Subramanian is drawn to the field. Sarcomas often strike children and young adults, who have so much life left to experience. Subramanian would like to discover ways to help these people. His own proposed title for this interview? “Let’s make sarcoma the disease of the past.”

Researchers look for tools that will allow doctors to better treat their patients. One recent example from Dr. Subramanian’s work was the discovery of a biomarker to distinguish between synovial sarcomas and malignant peripheral nerve sheath tumors. These two cancers can look very similar on imaging scans and under the microscope, but the best treatment for each type is very different.

Through your support, Rein in Sarcoma helps create the energy that sustains scientists like Dr. Subramanian. We thank you for this, and look forward to our future work together.

By Christin Garcia

Dr. Randy Hurley is a hematologist/oncologist at Regions Hospital and Medical Director of HealthPartners’ Cancer Care Program. He has been involved with Rein in Sarcoma since its onset. He was Karen Wyckoff’s medical oncologist and attended the very first RIS event with her. He has since attended nearly every Party in the Park and maintains a close relationship with Pete and Sue Wyckoff.

Dr. Hurley graduated from the University of Wisconsin – Madison with an undergraduate degree in Pharmacy. Before and during medical school, he worked as a clinical pharmacist on the hematology-oncology ward at the University of Wisconsin. He completed his internal medicine residency and chief resident year at UW as well. During this time, he was involved in basic science research on extracellular matrix proteins.

In 1991, Dr. Hurley came to the Twin Cities, where he completed a hematology-oncology fellowship at the University of Minnesota and spent an additional year investigating hematopoietic stem cell adhesion to extracellular matrix proteins. He has been at Regions Hospital for over 20 years, the past nine of which have been spent as the Medical Director of HealthPartners’ Cancer Care Program. Dr. Hurley also holds a special interest in global health. He is board-certified in tropical medicine and has had an ongoing health care project in Tanzania for 15 years.

Early influences in his career drew Dr. Hurley towards a career in hematology-oncology. Working with cancer patients, he says, is both an art and a science. His career provides both inspiration and challenge on a daily basis. According to Dr. Hurley, because sarcomas are so rare, many primary care physicians may not be familiar with how they present. This poses a unique health care challenge.

Dr. Hurley is leading a RIS pilot project at Regions Hospital and HealthPartners to increase awareness of sarcoma cancers among medical providers with the goal of significantly reducing the amount of time between the onset of sarcoma symptoms and a proper diagnosis. As a part of this effort, he is heading up a RIS Task Force with Robert Gao, 2016-17 Sarcoma Scholar; Brittany E. Mathews, Senior EPIC Specialist for HealthPartners Oncology Service Line; Tim Michalski, CEO of Point of Care Decision Support, Jay Syverson, President of Point of Care, Decision Support; Christian Ogilvie, MD, RIS Board of Directors; Pete and Sue Wyckoff. The Task Force is seeking to develop an electronic medical record alert to help Primary Care Physicians to recognize and appropriately evaluate suspicious soft tissue masses at an early stage. This pilot project is a key part of the efforts of the RIS Hallie Anne Brown Educational Initiative.

By Robert Gao, 2016-17 Sarcoma Scholar

I once heard University of Minnesota Associate Professor and medical oncologist Brenda Weigel referred to as “the hope doctor.” It is easy to see why this could be so. Dr. Weigel radiates a sincere and vital hope, fueled by her research seeking better cancer treatments but grounded in her experience treating cancer patients. “Far too often,” she has faced situations where there was “nothing else to do” for patients. But she also has seen recoveries in recent years that would have been unimaginable before.

Even more exciting developments are on the horizon. Dr. Weigel would like to recognize the Wyckoff family and all those who have helped Rein in Sarcoma, for the huge impact the group has had in moving the University to develop what is now becoming one of the premiere sarcoma programs in the country.

The Accidental Oncologist

It may surprise you to discover that Dr. Weigel “was not one of those people who knew from the beginning” that she wanted to be a doctor. She was “always interested in lots of things,” and chose to major in science in college. While obtaining her Masters degree in nutritional biochemistry, she worked at the Hospital for Sick Children in Toronto, Canada. In the late 1980s, as she pursued her graduate studies, a colleague suggested that she might try medical school instead. Her response? “Are you kidding me? I’d never get in!” But she did apply, and she did get in. Then she turned the offer down, because she wasn’t sure she really wanted to go. Dr. Weigel got married, and some time passed, and she began to think: “I may have made a big mistake.”

So Dr. Weigel applied again to medical school, and again she was accepted. She said to her husband, “I probably should do this!” Fortunately, then as now, her husband was wonderfully supportive. And so she went.

Dr. Weigel had loved working with children in the Toronto hospital, but she spent most of her time in medical school trying to convince herself that she would do something else. She was interested in “very intense fields” of medicine and had a strong interest in continuing to do cutting-edge scientific research. After she completed her internship, she realized that she had the most fun during her rotation through pediatrics. So she conducted her residency in pediatrics at the University of Western Ontario. She intended to go into critical care, practicing intensive care medicine.

Then, after a few months in an oncology rotation, “this light bulb turned on.” Dr. Weigel realized that pediatric oncology would allow her to marry her “love of research” with intense medicine, and also would allow her to develop “such incredible relationships with families,” which was something that critical care medicine did not offer.

In this way, an oncologist was born.

Onward, to Minnesota and Sarcoma

Very few options for oncology training were available in Canada, and someone suggested to Dr. Weigel that the University of Minnesota offered what she was seeking. So she and her husband traveled here early one November, when snow already was falling. Contrary to popular belief, Toronto is not quite so freezing as our great state. “The lake effect!”

After her interview here, Dr. Weigel was offered an oncology fellowship with full research funding for three to four years. This research guarantee sealed the deal, and she came in the mid-1990s. Her experience was “really really fantastic.”

Dr. Weigel landed in the lab of Dr. Bruce Blazar, a bone marrow transplant doctor who both worked to control immune system response after transplant and also to develop new ways to use the immune system to treat cancer. Dr. Weigel was drawn to solid tumors and particularly to sarcoma. At that time, the scientific literature was just “this black hole” with respect to sarcomas. Work simply was not being done, in this area “so desperately in need of research.”

So Dr. Weigel expressed her interest, and Dr. Blazar supported her completely. But she needed to blaze her own trail. She could use the lab resources, but she needed to “literally start from scratch” and figure out how to get it done. One has the sense that this challenge itself was a major draw. After weeks combing the literature, Dr. Weigel found a whole series of papers from the East Coast indicating that a cell line had been developed that could be used for research into rhabdomyosarcoma. She contacted Dr. Robert Evans, the retired man behind this work, and obtained his permission to carry on. He was “just incredibly gracious” and sent her the cells, happy to know that someone would use his work. And use his work, she and her University colleagues did.

When asked about what she is doing now, Dr. Weigel said that all her years in basic science research were “a gateway to bring new therapies to children and adults with cancer.” Now, most of her time is spent in early phase clinical trials and translational research, seeking to move new drug therapies out to people.

In talking about the course of her life, Dr. Weigel said she thought it important to “make the most out of whatever opportunity is put in front of you,” and to understand that “you never know what that opportunity will be.” The understanding she has gained through her work with patients and families has been important in shaping her scientific research. We are thankful that Dr. Weigel has poured so much of herself into both research and treatment, fulfilling a dual role she finds it “so crystal clear” must be played.

Hope on the Horizon

After so many years in the dark ages, it is astonishing to learn that sarcomas finally may be emerging into lighter times. Ten years ago, Dr. Weigel wrote a clinical trial design for young people with rhabdomyosarcoma. There were no new drugs available then; just a plan to deliver old drugs in new ways. In the first 18 months after the treatments were delivered, these changes allowed people to live longer overall and extended the length of time that they lived without return of their cancer. Even if the improvements fade away with more time, this is a great accomplishment. And there are promising signs that the benefits will stick.

Today, scientists have the technologies that will allow them to really study tumors in ways they never have been able to study them before. For example, Dr. Weigel and Bridget Charbonneau, a post-doctoral fellow with her colleague Julie Ross, have combed the tumor bank at the University of Minnesota to identify about 180 patients with synovial sarcoma. About 50 of these patients had good tumor tissue available for testing, and the team is looking for genetic markers that might tell them which tumors are more likely to be dangerous. If they can tell which cancers are more deadly, they can give the stronger treatments to those people facing the most danger. And if they can find the bad actors within the cells, they also might be able to develop drugs specially designed to target the cancer.

As science advances, more targeted drugs are becoming available that may hit the sarcoma tumors in ways that could really knock them out. With great folks like Dr. Weigel using this science, we have reason to hope.

When asked for her final thoughts, Dr. Weigel wished to highlight the impact that Rein in Sarcoma have had on the specific research in the field of sarcoma at the University. This, she said, “can’t go unrecognized.” She considers RIS to have been “a huge impetus behind what is now becoming one of the premiere sarcoma programs in the country.” This has been “spearheaded by the Wyckoffs,” and is an “incredible testament” to them and to the whole group of volunteers who have offered their talents and dedication.

By Christin Garcia

Dr. Cho has lived many places, but he does not feel adrift. He has lived in each place for quite some time, and always for a good reason. After growing up in the Washington DC area, he attended medical school at George Washington University and completed his residency there. He left for Duke University in North Carolina to begin his training in radiation oncology, but returned to George Washington University to complete it.

From there, Dr. Cho moved to Dallas to join the University of Texas Southwestern Medical Center and work with pre-eminent physician Dr. Eli Glatstein. Training under Dr. Gladstein was like “being a clerk for a Supreme Court Justice.” Dr. Glatstein was a good mentor and a fantastic leader. Dr. Cho gained experience with lung, prostate and breast cancer, in addition to sarcoma.

In 2005 Dr. Cho moved to Minnesota. He visited in September after enduring day after day of 100 degree Texas heat. Minnesota was beautiful and Dr. Cho thought he could live here in beauty all the time. As it happens, winter is cold and long and summer has too many mosquitos, but his family loves it here. And here he has stayed. Today, Dr. Cho’s practice includes the treatment of lung, prostate and sarcoma cancers.

“That’s Challenging”

Dr. Cho stumbled into radiation oncology, a field to which medical students had very little exposure when he was in school. He became involved in treating sarcomas and found them to be “very challenging stuff to treat.” Sarcomas involve every part of the body, and every body part has unique ways it can handle radiation. “Sarcoma is everywhere from head to toe – that’s challenging.” Targeting tumors while protecting healthy tissues is always the goal, and with sarcoma cancers the plans are unique to each person and different almost every time. “That’s what I like,” Dr. Cho said

He says that treating sarcoma cancers is “very challenging,” because they may appear anywhere in the body and often are located near critical body structures. In this work, as in life, each person is unique. Dr. Cho considers radiation oncology to be “a great field,” and he finds success in many different outcomes.

Clinical research is a big interest for Dr. Cho, who seeks to apply technology in different ways to improve outcomes. One cutting-edge tool is image guided stereotactic body radiotherapy, which can deliver precisely targeted beams. This is especially important for tumors, where the target location can change daily with normal fluctuations in the body.

In both prostate and lung cancer, doctors are studying new uses for radiation beams. Studies are being done to test the use of higher-dose and more precisely targeted radiation, given over several days instead of months. There are also ongoing studies comparing radiation head-to-head with surgery in lung cancer. Doctors look for short-term successes and problems, as well as long-term results. Some signs suggest that radiation therapy may be better than surgery, in certain cases. These technologies could be used with sarcoma, though the case would need to be chosen carefully.

Healthy Collaboration

At the University of Minnesota, doctors from many different fields all get together to talk about their sarcoma patients and decide which treatments would be best. The team has been meeting like this for years, and they are getting to the point where they “can almost guess what the other person is going to say.” All are “very comfortable expressing” an opinion, which leads to a great conference. The beauty about this is that each doctor is able to learn details and insights from the other specialists, leading to a well-informed and “healthy discussion” about how to treat. Most often, when the information is complete, the team can come to a consensus about what is best.

With sarcoma, of course, consensus is gained amidst uncertainty. There is a big open question, for example, about the best time to administer radiation. In Dr. Cho’s mind, pre-operative radiation is better. But better, he reminds us, “has to be defined collectively. What’s better for me is not better for Dr. Cheng.” When radiation is given before surgery, radiation oncologists can see their target better, decrease the dose and minimize the surrounding tissues that are affected. Yet pre-operative radiation can make surgery more difficult and doubles the wound healing problems after surgery. The best answer will vary for each patient, depending in part on the tumor size and location, as well as the important body structures located nearby.

Many Successes

Many outsiders consider radiation oncology to be a depressing field. Yet for half the patients, the doctors treat for a cure. “We want to get rid of it.” For the other half, treatment is designed to be palliative, which means to help with symptoms, pain and bleeding. “Each patient has a different goal,” Dr. Cho explains, and when pain is relieved, “we consider that a success.”

One difficult part of Dr. Cho’s job is trying to convey the vast amount of scientific literature about radiation therapy in a way that the patient understands and can accept. It is hard, for example, to explain the toxicities of radiation “without scaring them to death.”

And what is the good part? “When patients get better. That’s the reward.”

By Christin Garcia

Dr. Felasfa Wodajo was “humbled and honored” by our request to interview him, because he finds that “actually, it is the patients fighting sarcoma who are the real stories.” An orthopedic oncologist, now is a member of Virginia Cancer Specialists. He has lead the Musculoskeletal Tumor Program at Virginia Hospital Center. His Oncology Nurse Coordinator meets with patients and families, and likes to refer them to support groups and resources. She found the RIS Sarcoma Patient Starter Notebook on line. As Dr. Wodajo recalls, those books “lit us up” and they began offering the books to their patients. Some patients became so moved they decided to give back to RIS, and a great connection has been strengthened.

A long and winding road

Dr. Wodajo emigrated to the United States from Ethiopia in the fifth grade, and his family moved to the Washington DC area, where he now lives. He loves Ethiopia, which is a beautiful country, and recommends the book “Cutting for Stone.” There is a huge Ethiopian community in the DC area, which still includes many from his family.

His Minnesota ties? His wife was adopted into a second family while waiting tables as a teenager in Minnesota, then completed nursing school in the area. They have returned to Minnesota many times for family visits. “It doesn’t get any more Minnesota than that!”

He loved studying biology in high school and college, so thought he may become a scientist. The year after he graduated from Princeton, he immersed himself in a lab. He says it was “intellectually interesting but not for me.” He felt lonely and bored by himself all day, not interacting with other people.

He decided to go another way. At the University of California, San Francisco School of Medicine, as is typical, he rotated through many different fields of practice. As a medical student, “you sample everything.” In the end he decided on general surgery, and went into residency for this. He decided he preferred orthopedic surgery. A good choice, as it happens. Dr. Wodajo liked orthopedic surgery then, and he still loves it now.

During his orthopedic residency at Howard University, he rotated through many different practices within that specialty. Oncology grabbed him then. “Something lit up.”

Looking back, this makes sense. Orthopedic oncology brings back that biology interest. The way cells behave “makes enormous differences in outcome for patients.” It also presents interesting challenges. But it still maintains the mechanical aspect of orthopedics during reconstruction surgery, when doctors think about forces and vectors.

A really important part

But a primary reason Dr. Wodajo keeps doing this work is the person part of it. For this part of a person’s experience, orthopedic oncologic surgeons have a really important part. The way they do their work makes such a difference. Doing something big is not always best, and sometimes the most important job a doctor has is to hold back unnecessary or unhelpful interventions.

Sometimes, he says, “we do a great job, patients have great outcomes, and we feel like walking on water.” Yet one of the families most dear to him is the kids of a man who died of sarcoma. He was an “incredibly intelligent, remarkable man” with no good treatment options, and he and his family needed wise guidance as they navigated this path.

One thing doctors must do is to talk with patients and families about the hard news of sarcoma. Doctors need to be blunt, conveying information in a way that they are not lying about a person’s condition or chances. But “there is a very long distance between blunt and harsh.” It is important to understand that “statistics are not predictive, they’re only descriptive.” Statistics like survival percentages are a piece of information, but people should know “it may not be as helpful as you think it is.” The true reality is the wide variation in different people with unique circumstances who have individual outcomes.

In the broadest sense, it is challenging to make the right decision, to know what to do. There are many options, and it is frustrating that there is so much room for the options to improve. Doctors who treat sarcoma patients wish they had better techniques, better implants, better chemotherapy. They wish they could do more. But it isn’t helpful to say that to the patients who sit in front of them.

I told Dr. Wodajo he could say it to us, because we at Rein in Sarcoma are well enough aware of the limits, but also are invested hopefully in changing the future.

Raising awareness

In the Washington area, orthopedic oncologists don’t see very many cases where a general surgeon has operated on a sarcoma without knowing it. He’s not sure why, but said “I’m happy about that.”

Perhaps one reason is an oncology review course Dr. Wodajo has presented annually for the last twelve years. Each class reaches 20 to 30 orthopedic residents in the region, and “each of those is a multiplier,” going out into the world to share their knowledge. A spark for the future: perhaps it would be important to reach general surgery and family practice residents too, because they may present the first contact for patients, but may not encounter sarcoma more than once or twice in their career.

As we know, each contact is important. Each moment may be sacred. So we very much appreciate teams like this Virginia team and leaders like Dr. Wodajo. Thank you for this work!

By Christin Garcia