C O L L A B O R AT I N G
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C O N Q U E R
C A N C E R
04: WHAT IS CANCER? 12: Q&A WITH BREELYN WILKY, MD 13: C3 MD BRAD CORR, MD 14: DID WE DO THE RIGHT THING? 18: THE GEOGRAPHY OF CANCER IN COLORADO
WHAT IS CANCER? UNIVERSITY OF COLORADO ANSCHUTZ MEDICAL CAMPUS
N WS How human genetic data could help dogs fight canCER Some of what we learn through the compassionate treatment of dogs with cancer goes on to help human patients. Now CU Cancer Center researchers at Colorado State University Flint Animal Cancer Center are returning the favor: By sequencing 33 canine cancer cell lines to identify “human” genetic changes driving these canine cancers, researchers hope to find more human medicines that could cure cancer in dogs. “We’re taking what we know from human cancers and applying it in canine cancers to help move the canine cancer treatment forward faster,” says Dawn L. Duval, PhD, investigator at CU Cancer Center and assistant professor in the CSU College of Veterinary Medicine and Biomedical Sciences. Then, by determining which canine cancers are most like human cancers, the group may also be able to transfer lessons learned while treating these human-like canine cancers back to the treatment of human patients. “This would allow us to treat dogs in clinical trials in a way that could be used to improve therapies for both species,” Duval says.
Combined breast and gynecologic surgery: Study says not so fast Breast cancer patients and women undergoing cancer-preventive breast surgeries may consider
can delay the start of important chemotherapy. “This is something I talk with patients about
combining these procedures with hysterectomy and/
on a weekly basis. Patients have the impression,
or ovarian removal. However, a CU Cancer Center
‘I just want to have one surgery and have
study published in Breast Journal argues against this
everything done.’ But complication rates are
combined approach: Patients undergoing coordi-
higher with that approach. In patients at high risk
nated breast and gynecologic procedures had a
of developing breast cancer and ovarian cancer,
significantly longer length of hospital stay, and higher
we recommend doing the prophylactic bilateral
complication, readmission, and reoperation rates
mastectomy along with breast reconstruction,
compared with patients who underwent single site
but then trying to keep gynecologic surgery
surgery. In addition to a higher rate of complications,
separate. It’s safer and easier to do them
the challenge of coordinating breast, reconstructive,
separately,” says Sarah Tevis, MD, CU Cancer
and gynecologic surgeons may lead to treatment
Center investigator and breast surgeon at
delays, while longer recovery from combined surgery
UCHealth University of Colorado Hospital.
SARAH TEVI S, MD
294 days between symptoms and diagnosis of colorectal cancer in young patients
Get more CU Cancer Center news on our blog: www.coloradocancerblogs.org Subscribe for updates on the latest research, news, and events.
The incidence of early onset colorectal cancer has increased nearly 50 percent in the last 30 years. A CU Cancer Center study found that many of these cancers are diagnosed at a late stage, after significant delay in the process of diagnosis. More than half of 173 patients studied presented with rectal bleeding before diagnosis. On average, 294 days passed between the first time the patient noticed rectal bleeding and the time they were diagnosed. By the time of diagnosis, 37.8 percent of the patients were Stage IV. “Our results show that young adult patients present with a much higher rate of Stage IV colorectal cancer compared to patients who are older,” says Gurprataap Sandhu, MD, fellow at the CU Cancer Center. “Patients and primary care physicians should be made aware of this finding in order to facilitate timely referral for colonoscopy which may lead to earlier diagnosis, less advanced disease at diagnosis, and improved outcomes.”
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PROMISING outreach
Nobel Laureate, Tom Cech, PhD, suggests new way to target third most common oncogene, TERT Cancers like melanoma, glioblastoma, and bladder cancers almost universally over-activate a gene called TERT. Unfortunately, despite a massive research effort, TERT inhibitors have been largely ineffective. Now a study
“Mir acle drug” helps patient with recurring prostate cancer find his inner poet
by Nobel Laureate, Thomas Cech, PhD, CU Cancer Center investigator and Director of the Biofrontiers
After being told for the third time that his prostate cancer
Institute at University of Colorado
had resumed growing, Jonathan Ormes, who had graduated
Boulder, shows that unlike other
from Stanford University and worked for NASA for 37 years,
genes, the messengers in charge of
chose Dr. Thomas Flaig, MD, CU Cancer Center investigator
transporting TERT blueprints to a cell’s
and associate dean for clinical research at the University of
manufacturing centers tend to get hung
Colorado School of Medicine as his last-chance doctor. After
up in the cell nucleus.
unsuccessful hormone therapy, Ormes and Flaig decided on
TO M CECH, PHD
“Our hypothesis is that there’s a special mechanism for transporting TERT mRNA that is really slow or inefficient – and if that’s the case, maybe that could be a new
a clinical trial. “Thanks to the drugs they have prescribed I am very lucky to be leading a pretty normal life,” Ormes says. “My PSA levels are low, and my side effects are quite manageable. I am actually feeling better now than I have in a long while.” One side-effect that Ormes was not expecting was the
target for interfering with the action of TERT. Maybe we could attack TERT in cancer cells by keeping mRNA trapped in the nucleus,” Cech says. In other words, maybe the silver bullet in the fight against TERT over-activation has nothing to do with TERT over-activation at all. If we could trap TERT messengers in the nucleus, it wouldn’t matter how over-activated the gene is – if the blueprints
desire to write about his cancer experience. As part of a
can’t leave the nucleus, the gene would never be manufactured into its cancer-
prostate cancer support group, “We had the opportunity to
causing product.
go to a writer’s workshop, so I figured why not?” says Ormes. “That experience was probably the neatest thing to happen about learning I have two to three years to live when I was first
Evelinn Borr ayo, PhD, brings experience, ideas to healing the cancer care divide in Color ado
diagnosed. It was a very humbling moment.”
“There are people in underserved communities and in rural areas in Colorado that are
to me during my time in the support group. I wrote a poem
dying of cancers that are preventable and treatable,” says Evelinn Borrayo, PhD, the Here is an excerpt from Ormes’ poem, Prognosis:
newly appointed Associate Director for Community Outreach and Engagement at CU Cancer Center. Her goal is to decrease these cancer disparities – to make sure that everyone in Colorado has equal access to cancer prevention and treatment.
Your cancer has spread
“It doesn’t matter that we’re developing new, effective treatments if you can’t
I’m compelled to ask.
access them,” Borrayo says.
Prognosis?
Cancer maps (see page 19) show that areas of Colorado’s Eastern Plains,
You might live two or three,
Western Slope and far south have rates of cancer incidence and outcomes similar to
but who knows.
those in Appalachia. On the other hand, the Front Range and mountain communities I fear not dying.
along the I-70 corridor have cancer outcomes far better than national averages. While
I’ve lived well.
CU Cancer Center scientists are developing new treatments to raise the ceiling of
It’s pain that threatens,
cancer care, Evelinn Borrayo will be working to ensure that underserved communities
I volunteer
aren’t left in the basement.
Doctor kindly “We have ways of managing it.” My wife is crying. My thoughts turn to the grim reaper.
J ON AT H A N OR M E S
“It doesn’t matter that we’re developing new, effective treatments if you can’t access them.” “We’re working with people in these communities to understand what their
I implore
barriers are,” Borrayo says. “Then, person-by-person, we are removing these
“Don’t wave your dull blade of fear
barriers to cancer prevention and care.”
Use the sharp blade of certainty. Your scythe once wielded, make it true.”
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WHAT IS CANCER? BY GARTH SUNDEM
On a sunny fall Saturday after a CU Buffs win, my 13-year-old, Leif, and I walked down to Boulder’s Pearl Street Mall to talk with strangers about cancer. Among others, we spoke with a mid-60s visiting Arizona State football fan, a very cute eight-year-old girl, and some guy with dreadlocks named Carl. We asked them three questions: What is cancer, How do you get cancer, and How do you treat cancer? I also asked these same questions of University of Colorado Cancer Center researchers including Nobel Laureate, Tom Cech, PhD, director of the CU Boulder BioFrontiers Institute, and D. Ross Camidge, MD, PhD, Joyce Zeff Chair in Lung Cancer Research and Director of the CU Thoracic Oncology Clinical and Clinical Research Programs. Can you guess who said what?
WHAT IS CANCER?
“The uncontrolled growth of some of our cells.”
“Cancer is a scary disease.”
Carl represents the majority of answers, which included some combination of the words DNA, mutation, and tumor. Tom Cech, winner of the 1989 Nobel Prize in Chemistry, said that cancer is uncontrolled cell growth, and D. Ross Camidge similarly said that cancer is a cellular mutiny. Of course, Drs. Cech and Camidge are correct and we’ll get to their definitions of cancer in a minute, but it’s the 8-year-old’s answer that gets to the real point: Cancer is a scary disease. We care about cancer not because of what it is, but because of what it does. But the more you know about what it is, the more you can understand what it does. And in some way, maybe that can make it less scary. If you’re a patient or caregiver or even a researcher who believes knowledge of cancer is power over cancer, read on. Let’s start the real definition of cancer by looking at what it’s not. It’s not like other diseases. You can’t catch it. There is no tiny bacteria or virus or fungus that causes cancer (okay, there are infections like HPV that increase cancer risk, but that’s slightly different). Instead, cancer is just a mistake. This scary disease starts as a tiny mistake in one of your body’s 37.2 trillion cells.
“A cellular mutiny.”
“When your DNA mutates and it makes tumors.”
Whether blood cancer, bone cancer, breast cancer, or any of the cancers affecting the body’s many other types of tissues, cancer is the mistake of uncontrolled growth by mutinous cells. If we’re being nitpicky here, cancer is actually the uncontrolled replication of cells – because it’s not that a single cancer cell swells into a tumor, but that a cancer cell spits out dangerous little copies of itself that all clump together into a mass (or blossom through the blood). Really, by itself, we don’t care much about a tumor – you could implant a baseball under your skin and it probably wouldn’t kill you (though remains contraindicated in most cases). The problem is that tumors are like cars broken down on I-70 in the middle of the weekday commute – simply by being there, they can block digestive or cardiovascular systems. Or cancer cells can push out healthy cells in essential structures like the liver, blood, or bones. The mistakes that cause cancer happen in your genes. Remember, genes are blueprints. Sometimes the cancer-causing mistake is the simple scrambling of a gene’s blueprint (genetic mutation), and sometimes bits of genes are mashed together to make a dangerous
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new blueprint (genetic fusion), and other times a gene’s blueprint is manufactured too often or not often enough (genetic amplification, downregulation, etc.), but the result is the same: Genetic mistakes lead the body to manufacture stuff that tells cancer cells to grow, divide, and survive without bounds. Of course, this makes it sound like cancer is one disease, caused by a single genetic mistake that happens to pop up in a certain part of the body like the lung or breast or prostate, but that’s not the case at all. Cancer can be caused by many different genetic mistakes, and most cancers have more than one mistake. This means that there are many different kinds of cancer, defined not only by where they live in the body, but by the genetic mistakes that create them. There’s ALK cancer, ROS1 cancer, BRAF cancer, BRCA cancer, MYC cancer, and many more, with hundreds or even thousands still waiting to be discovered. Cancer is not one disease, but many related diseases. What do they all have in common? Drs. Camidge and Cech said it: No matter the genetic mistakes that causes cancer, the result is uncontrolled growth of mutinous cells. Or if you prefer to keep it simple, cancer is a scary disease.
HOW DO WE GET CANCER?
“From the sun and smoking and eating burned meat.”
“Normal cellular behavior can be disturbed by environmental factors that alter our DNA or due to normal errors that occur in DNA every time a cell divides.”
“Something goes wrong in your body.”
“We don’t know. Some people seem like they should get it and don’t. Other people seem like they’d never get it and they do.”
“Mostly mutations, which can be caused by environmental insults, or spontaneous, or inherited.”
Genetic mistakes cause cancer, but what causes these genetic mistakes? In fact, all these quotes are correct. Carl is correct that exposures to things like the sun and smoking make DNA errors more likely (the jury’s still out on burned meat); D. Ross Camidge and Tom Cech are correct to add cell division errors (like a broken copy machine) and mutations that we get from our parents to Carl’s list; and our 60-something Arizona football fan is correct that despite these risk factors, who gets cancer still comes down to chance. Again, our 8-year-old sums it up: You get cancer when something goes wrong in your body.
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But the creation of a cancer cell is only half the story. In fact, work at CU Cancer Center and elsewhere shows that cancer cells pop into existence all the time (as if you needed another reason not to sleep at night). Most of these cancer cells are killed immediately – the body has systems that specialize in recognizing cells with altered or damaged DNA and then either repairing the damage or, if the damage is beyond repair, killing the cell. Then there’s the role of the immune system – if a cancer cell looks different enough than a healthy cell, the immune system may recognize it and kill it. Finally, there’s the harsh truth of natural selection. See, the fact is that we largely overestimate the strength of cancer cells. Sure, they replicate really fast, but the genetic mistakes that produce this superpower also make them an imperfect match for the ecosystem of the body. Think of it this way: The great white shark may be nature’s ultimate predator, but they tend to
have non-optimal survival outcomes compared to camels when placed in the Sahara. If the body is the Sahara, healthy cells are camels and cancer cells are the sharks. And in the ecosystem of the body, healthy cells tend to out-compete cancer cells. What this means is that even though we develop cancer cells all the time, we rarely get cancer. Not until, as CU Cancer Center Deputy Director, James DeGregori, PhD, shows, there’s a different playing field. Not only do risk factors like smoking and alcohol use insult DNA in a way that increases the accidental production of cancer cells, they change the ecosystem in which cancer cells compete against healthy cells. It’s like submerging the Sahara. In a tissue ecosystem damaged by age, sun, smoking, etc., suddenly highly adaptable, quick-growth cancer cells (sharks) may find themselves more fit than healthy cells (camels). Or, as our 8-year old said, something goes wrong in your body.
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HOW DO WE TREAT CANCER?
“If we can remove all the mutinous cells with surgery that’s obvious. Sometimes we can kill them in place with radiation, and sometimes we use drugs.”
“You go to the doctor.” “Immunotherapy is the new breakthrough – unleashing your own immune system to destroy cancer cells.”
“By poisoning yourself to the edge of death.”
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Interestingly, it was our 60-something football fan and not Carl who said the secret to treating cancer is to poison yourself. In a way he’s right: Chemotherapy pushes all your cells toward the edge of a cliff, and because cancer cells start closer to the edge, the hope is that more cancer cells than healthy cells take the plunge. But while chemotherapy remains part of the best treatment for many cancers, we live in a renaissance of new strategies against cancer that can augment or even replace traditional strategies. But let’s back up a step. You’ve heard the old saying about the horse and the barn door. Similar is true of cancer: The best way to treat cancer is to lock the barn door before the horse escapes – in other words, to prevent it, most importantly by avoiding known risk factors. Barring that, the next best option is to catch
the darn horse before it goes too far. If a mammogram can catch breast cancer as stage 1 disease (when the cancer is contained in the breast), the 5-year survival rate is 99 percent; but if breast cancer is detected only once it’s spread (stage 4 disease), the 5-year survival rate is only 27 percent. With colon cancer, screening via colonoscopy can detect and treat cancer before it’s even cancer, removing pre-cancerous polyps. And lung cancer screening for high-risk populations is becoming more and more accessible. (Emerging screening techniques seek to sample blood, breath, or stool for molecular signatures of cancer cells.) The gist is that no matter how a cancer is treated, catching it earlier is better. Which, of course, does about as much good for a cancer patient as telling a farmer with a lost horse that he should have locked the barn door. Let’s say you have cancer. What now? Well, as our 8-year-old said, you go to the doctor. Actually, because no single doctor does surgery, radiation, and drugs, cancer patients go to many doctors. When you go to these doctors, they will help you decide what kinds of treatments meet your goals. Some cancers grow so slowly that you’re more likely to die with them than from them, and thus don’t require treatment. Others can be surgically removed. Some will require chemotherapy before or after surgery. Sometimes radiation replaces or augments surgery and/or chemotherapy, or radiation can be used to zap pockets of disease that recur after other treatments. Then there are drugs beyond chemotherapy. Remember that cancers are caused by genetic mistakes, and now many genetically targeted drugs turn off these mistaken genes. Or drugs may restrict the things that cells with malfunctioning genes need, for example withholding estrogen from estrogen-addicted breast cancer, or withholding androgen from androgen-addicted prostate cancer. And as Tom Cech suggests, immunotherapy is a game-changer for many kinds of cancer. Cancer treatment was never simple, and now with innovative scientists and doctors coming at cancer from new directions that were entirely unimaginable a decade ago, treatment can be mind-bogglingly complex, with new layers of complexity – along with new reasons for hope – coming down the drug-development pipeline seemingly every day. This is why is takes over a decade of school and training to become a cancer doctor, and why CU Cancer Center gathers over 300 of these MD, PhD, MPH, and other specialists, each adding their unique expertise to the study and treatment of this family of related diseases. So cancer is the uncontrolled growth of mutinous cells that outcompete healthy cells in the ecosystem of the body, and is treated with complex combinations of space-age treatments. Or you can understand it this way: What is cancer? It’s a scary disease. How do you get cancer? Something goes wrong in your body. How do you treat cancer? You go to the doctor. It turns out that all we really needed to know about cancer comes from an 8-year-old on the Pearl Street Mall.
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DEC
DING CANCER Look closely! Can you sort the cancer cells from the healthy cells? (Answers below) 4
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Key: 1. Skin cancer cells; 2. Cancer cells with RAS gene changes; 3. Healthy stomach cells; 4. Healthy mammary glad cells; 5. Metastatic melanoma cells; 6. Normal lung tissue; 7. Breast cancer cells; 8. Osteosarcoma cells; 9. Ovarian cancer cells (HELA)
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A CONVERSATION WITH BREELYN WILKY, MD CU Cancer Center Deputy Associate Director for Clinical Research
B Y T AY L O R A B A R C A
After five years as an assistant professor at the University of Miami treating sarcoma patients and running sarcoma clinical trials, Breelyn Wilky, MD, recently joined University of Colorado Cancer Center as Deputy Associate Director for Clinical Research. Here we speak with Wilky about what drew her to Colorado and what’s next for the treatment of sarcoma.
C3: Sarcomas represent only about 1 percent of all cancers. What made you want to study this rare disease?
became passionate about trying to figure out
away in certain cases. It’s really incredible.
how to make immunotherapy work for more
We are focusing on trying to understand
patients. The CU Cancer Center appealed to
why checkpoint inhibitors are so successful
me because it has an outstanding sarcoma
in these patients in hopes of being able to
Wilky: When I was just starting my fellowship
program with a large catchment area and
expand them to other patients. In fact, I’m
at Johns Hopkins, I had several young
also a huge push for immunology research,
excited to be leading several cutting-edge
patients with sarcoma. I remember searching
especially with the recruitment of Terry Fry,
immunotherapy clinical trials for sarcomas
the NCCN guidelines, PubMed, and Google
MD, and Eduardo Davila, MD. These two
here. We’re about to open an investigator-
trying to find options for these patients and
faculty have provided incredible mentorship
initiated clinical trial combining doxorubicin,
was incredibly disappointed with the results.
and support as I’ve gotten up and running
the standard of care, with two immune
The challenging part of sarcoma is that if
here. I couldn’t imagine being anywhere else!
checkpoint inhibitors for soft tissue sarcomas.
surgery can’t be done, treatments for the patients and survival are usually very limited. I felt that any small contribution I might make for sarcoma patients could have a huge impact on them and the way the disease is treated.
C3: What convinced you that University of Colorado Cancer Center would be the best place to work on sarcoma?
Additionally, we are a site for several industry-
C3: It seems like an exciting time for many cancers, with new targeted treatments and immunotherapies offering options for patients who might have had a poor prognosis even a couple years ago. Have these kinds of new treatments reached sarcoma, as well? Wilky: Unfortunately, change has remained
Wilky: While in Miami, I conducted my
slow since I was in fellowship. On the one
first investigator-initiated clinical trial with
hand, genetic testing and genomics have
immunotherapy for sarcomas, and really
been essential in helping us focus on targeted
to help bring laboratory science to first-inhuman clinical trials. So, yes, I’m hopeful that new treatments are on the way!
C3: Congratulations on being named Deputy Associate Director for Clinical Research! What are you most excited about this role? What does the role entail? Wilky: I am super excited to take on this role, which will allow me to be a part of CU Cancer Center’s efforts to expand our
However most adult-type sarcomas are still
clinical research initiatives. My role is focused
being treated with the drug doxorubicin,
on leading the Investigator Initiated Trial
which has been the same since the 1970s.
(IIT) committee and team. This incredible
Wilky: The role of immunotherapy in sarcomas really is the next frontier and we have really just begun to explore it. Right now, these treatments are helping only a small population of patients but when it does, it is the real deal. I have seen checkpoint inhibitor immunotherapy literally “melt” the disease
WWW.COLORADOCANCERCENTER.ORG
be partnering with our laboratory researchers
therapies for certain types of sarcoma.
C3: Do you see this changing – are there new treatments on the horizon?
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sponsored clinical trials. Finally, I’m excited to
infrastructure is designed to expedite ideas that come from our own investigators, not from outside pharmaceutical companies. These can be first-in-human trials of technology developed in our laboratories, or new combinations of existing drugs that have not been explored before. An investigator-initiated trial is really the holy grail of bench to bedside research, and I couldn’t be happier to lead this.
A Slippery Slope to the Operating Room
MD
CLINICAL
CARE
BRAD CORR TAKES A NONTRADITIONAL PATH TO CANCER RESEARCH AND CARE B Y TAY L O R A BA R C A Brad Corr’s inspiration to pursue a medical career
here as a fellow, I thought it was an outstanding
came on the ski slopes of Big Sky, Montana.
program. Since then, the program has developed
“After an undergraduate degree in geology and physics, I went to Montana to be a ski patroller. “My role in helping people on the
tremendously. It has been terrific to be a part of the growth and help the division continue to grow.” Corr’s role as the division’s Director of Clinical
slopes really affirmed my desire to go to medical
Research allows him to combine clinical care
school,” explains Corr. “You could say I went the
with research.
nontraditional route to medical school.” In addition to helping people, Corr, who grew
“It kind of brings me full circle, back to my love of science. Now I can lead research into new
up in the suburbs of New York City, was always
strategies against cancer, in addition to practicing
drawn to the science behind medicine.
medicine,” says Corr, who is also one of the lead
“What truly made me want to be a doctor
gynecologic oncologists on the CU Cancer Center
was the science of it in addition to the patient
Women’s Cancer Developmental Therapeutics
care aspect,” he says.
Program. “I really enjoy working with patients
Now a longer drive from the ski slopes,
on clinical trials. We are in a phase of oncology
Corr, MD, is a CU Cancer Center member and
research where there is so much development in
was recently named Director of Clinical Research
novel therapies. It is exciting to be on the forefront
for CU School of Medicine Division of Gynecologic
of it.”Corr is not only at the forefront of new
Oncology, the largest group of physicians in the
developments in endometrial cancer, he is leading
Rocky Mountain Region dedicated to women’s
the charge – one of his current clinical trials seeks
cancer care.
to change the way we treat the disease.
“It was the combination of medicine, surgery
Rucaparib is an FDA-approved drug that
and the continuity of getting to know patients over
works by turning off a gene called PARP. However,
time that attracted me to the specialty,” he says.
research by Corr and others has shown that
“Gynecologic oncology gives me the opportunity
patients with changes in a gene called PTEN may
to be with the patient through the entirety of their
also respond to rucaparib, and PTEN mutations
disease course. I am the one prescribing their
are found in over 80 percent of endometrial
treatments, doing the surgeries, and following up
cancers. Corr’s phase 2 clinical trial is testing
with patients after their treatment is over. It really is
rucaparib as maintenance therapy for patients
the entire package.”
with metastatic or recurrent endometrial cancer
Corr and his wife, who is a primary care doctor, made the move to Colorado in 2013. “Growing up I vacationed in Colorado frequently. I fell in love with the atmosphere and
BRAD CORR, MD, AND FAMILY
that have been treated initially with chemotherapy. This trial is one of the first to use PARP inhibitors in endometrial cancer. “I believe that this clinical trial could be
outdoor way of life. I always aspired to live in
a foundational step toward practice-changing
the state,” says Corr. “Although the Division of
therapy,” says Corr. “There are currently no
Gynecologic Oncology was young when I started
approved maintenance therapies in endometrial
cancer, and if this trial demonstrates similar success rates to what we have seen in ovarian cancer, I believe this drug, or another drug in the class of PARP inhibitors, could become part of the standard of care for some patients.” Although his researched is heavily focused on endometrial cancer, Corr cares for patients with all different types of gynecologic cancers at different stages. Taking on these cases can be challenging, but also incredibly rewarding. “Unfortunately, many of the patients I see believe that they are going to die very shortly,” he says. “Often, I get to change that mentality. Some of the patients I see are actually able to be cured, while others get more quality time that they never expected. Those are the moments that are gratifying as an oncologist.” How Colorado is that? A ski patroller turned leader in cancer research? But sometimes it takes a unique perspective, trained in science, testing in the mountains, and honed in the operating room, to truly push the boundaries of medicine.
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“Did We Do the
Right Thing?”
NICOLE AND DAVID GARRETT FACE THE QUESTION OF FERTILITY PRESERVATION IN THEIR 4-YEAR-OLD BY TAYLOR ABARCA It’s every parent’s worst nightmare. “Your child has cancer.” For Nicole and David Garrett, this nightmare became a reality in September 2014. Within days of the diagnosis they were faced with dozens of questions that would have lasting effects on their four year old son, Corbin. With all of the decisions to be made, one that caught them by surprise was the future of their potential grandchildren. The option to preserve fertility before starting cancer treatment is something most parents have never discussed, or even thought about. For the Garretts, the decision of whether or not to preserve their son’s fertility was, in their words “fast and informal.” Now, nearly five years out from the final treatment, Nicole and David find themselves wondering what many parents in their situation might wonder: “Did we do the right thing?”
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More Than a Tummy Ache When Corbin was four years old, he suffered from a common ailment in children his age: constipation. So, when Nicole was rubbing his stomach and felt something hard, she assumed he was just stopped up again. “Corbin had been to the doctor numerous times to take care of his irregularity,” says Nicole. “I truly didn’t think it was anything to be concerned about. I remember having family over for the Bronco’s game that evening and asking if they think I should be concerned. The unanimous answer was ‘no.’” However, when the lump felt bigger the next day, the Garretts decided to take Corbin into Children’s Hospital Colorado to be checked. “We were taken aback to have an ultrasound. Then during the ultrasound, the radiologist didn’t say anything, which I thought was odd,” says Nicole. “When they were done, they asked Corbin to pick something out of the toy chest. They had never done this before. That’s when I got the feeling something was not right.” Nicole’s gut feeling was correct. A tumor the size of a grapefruit had been hiding and growing in Corbin’s abdomen. “After the ultrasound, a doctor came to talk with my husband and me. I remember him saying that he was an oncologist. I can’t believe I am saying this now, but at the time I had no idea what an oncologist was,” says Nicole. “It took a few minutes for me to register that Corbin had cancer.”
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Tiny Fighter At only four years old, and just starting preschool, Corbin had Burkitt’s Lymphoma, a fast-growing cancer in the body’s lymphatic system. “It was such a crazy night. We thought we were going in for a diagnosis of constipation and the next thing we knew we were being admitted to the hospital for cancer,” says Nicole. “It was such a blur. Corbin had to be poked, prodded, and tested for all types of things to get more information. David and I were in shock.” Over the next few days, Corbin’s care team developed a treatment plan and were ready to get started. However, among a million other decisions, Nicole and David had an unexpected decision to make: whether or not to preserve Corbin’s fertility. “At that time there was so much going on and so many documents to be filled out that when the question came up, we weren’t sure what to do,” says Nicole. “It caught us off guard to be talking about saving Corbin’s sperm when he was so young. It’s something most parents don’t talk about.” It’s not just parents who tend to overlook fertility preservation. According to a study from the Journal of Adolescent and Young Adult Oncology, less than 5 percent of young women and 43 percent of young men are seen by a reproductive specialist before treatment. The gender difference is due mostly to the ease of collecting sperm compared with the difficulty of preserving eggs, the latter of which can delay the start of treatment by as much as two weeks. Still, in prepubescent male patients who are not yet producing sperm, fertility preservation requires banking testicular
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CORBIN KEEPS IT POSITIVE DURING TREATMENT tissue with the hope that in the future when the child wants to start a family, science will have developed a way to use stem cells inside this tissue to generate sperm. The difficulty and uncertainty of fertility preservation in prepubescent boys means that the question of future fertility often takes a backseat to the more pressing concern of immediate survival.
Preserving Fertility Pediatric cancer used to be a death sentence. But now the survival rate is about 90 percent, and with so many young patients going on to live full lives after treatment, quality of life issues are increasingly important. Now the question is not just whether a child will live after cancer, but how they will live. This is where programs such as the CU Cancer Center Oncofertility Program come in. Certain types of chemotherapy and radiation can cause damage to the reproductive organs in both males and females. Although these treatments are necessary and lifesaving, they may lead to infertility or inability to have children in the future. Launched in 2012, the Oncofertility Program at CU Cancer Center offers fertility preservation procedures such as freezing sperm, eggs, or testicular/ovarian tissue before treatment begins. By freezing the reproductive cells, patients going through cancer have the opportunity to use them in the future should they choose to have children. If a patient has already completed cancer therapy, the program can help with in vitro fertilization, egg donation, or even surrogacy options. CU Cancer Center’s Oncofertility Program is one of only a handful in the United States that provide a multidisciplinary approach to cancer treatment planning and care. The program helps young patients and their families create short-term and long-term reproductive plans with the help of fertility preservation doctors. These plans usually start before cancer treatment begins and finish long after the treatment plan ends. In some cases, reproductive plans can start after treatment is completed. In other cases, the plan has to come first.
CORBIN, NICOLE, DAVID, AND ADDYSON
The Right Decision In Corbin’s case, the decision whether or not to preserve fertility was a tough one. “If we had gone forward with preserving his fertility it would have delayed starting treatment,” says Nicole. “We couldn’t help but wonder if delaying treatment, even for just a couple of days, would affect his prognosis. We decided that it was not worth the risk.” In the end, Nicole and David decided not to go through with fertility preservation for Corbin. Now, Corbin is cancer free and nearly five years out from his last treatment. Looking at him, you would never believe he once was fighting for his life. When he is not out on the ice playing hockey, he enjoys hanging out with friends and bugging his little sister. “As he gets older, I do wonder sometimes if we made the right decision,” says Nicole. “I try not to worry about it though. In the end, I believe we made the best decision we could at the time. We have a healthy boy who gets to grow up. His ability to have kids is something we will deal with in the future.”
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THE GEOGRAPHY OF CANCER IN COLORADO Is where you live going to kill you?
BY GARTH SUNDEM
Cross your fingers for an easy drive through Vail Pass and the Eisenhower Tunnel and let’s take a road trip across Colorado. According to the Centers for Disease Control and Prevention, in Mesa County on Colorado’s Western border with Utah, every year about 410 of every 100,000 people are diagnosed with cancer. But drive a couple hours east to Summit County and that rate drops by more than 40 percent, down to 241 cases of cancer for every 100,000 residents. And by the time you’re out east in Kiowa County along the Kansas border, the cancer rate is back up to 487 per 100,000 people, double that of Summit. Sure, you say, that must be because young people are drawn to recreational opportunities in Summit County, leading to a younger population that gets less cancer. But that’s not the case. The median age in Summit County is 39.2, while the median age in Mesa County is 39. It’s not age – something else is going on here. The fact is that not only does where you live influence whether you get cancer, but it can influence whether you survive cancer, too. In Summit County, the cancer death rate is 30 percent of the cancer diagnosis rate. In Kiowa County, the cancer death rate is 54 percent of the diagnosis rate. The combination of higher diagnosis rate with higher death rate means that people living in Kiowa County are almost four times as likely as people living in Summit County to die of cancer. Let’s look at why.
EXPOSURES At the risk of stating the obvious, where you live in large part determines what you breathe, eat, drink, and absorb. For example, because residents of Summit County live at altitude (and like to go outside), they are exposed to over-average levels of UV
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radiation, and while their overall cancer rate is low, the rate of melanoma and other skin cancers in Summit County is sky high – almost double that of lower-elevation Mesa County. Of course, there are many other environmental exposures that can increase cancer risk. For example, you wouldn’t have wanted to live near Chernobyl in 1986, asbestos exposure causes mesothelioma, and occupations such as roofing and aluminum production increase exposure to cancer-causing polycyclic aromatic hydrocarbons (PAHs). Here in Colorado, we have a state-wide risk of radon exposure, and preliminary evidence by Colorado researchers published in the journal PLoS ONE shows that living near oil and gas development may increase the risk of childhood blood cancers. But these risks aren’t nearly enough to explain the disparities in cancer diagnosis and death rates across counties. For that, we need to leave the environment and start looking at people.
MORTALITY RATES BY COUNTY Sedgwick Logan
Larimer
Jackson
Moffat
Phillips Weld
Routt
Morgan Grand
Boulder
Rio Blanco
Larimer
Jackson
Moffat Routt
Gilpin
Grand
Pitkin
Mesa
Lake
Park
Eagle
Garfield
Delta
Summit
Pitkin
Lake
Dolores
Montezuma
Montezuma
Arapahoe
Kit Carson
Lincoln Cheyenne
El Paso
Kit Carson
Elbert
La Plata
Pueblo
Custer Fremont
Saguache
Kiowa
Huefano Alamosa
Rio Grande Mineral
Bent
Prowers
Huefano
Conejos Archuleta
Otero
Prowers
Bent
Otero
Pueblo
Custer
Hinsdale Mineral
Archuleta
Kiowa
Cheyenne
Crowley
Crowley
Ouray
San Juan
El Paso
Teller
Chafee
Rio Grande
La Plata
Yuma
Washington
Park
Saguache
Ouray Montrose Hinsdale San Juan
Elbert
Adams
Lincoln
Gunnison
San Miguel
Broomfield Douglas
Fremont
Delta
Dolores
Morgan
Teller Douglas
Montrose
San Miguel
Arapahoe
Clear Denver Creek Jefferson
Chafee
Gunnison
Mesa
Gilpin
Phillips
Weld
Boulder
Rio Blanco
Yuma
Logan Washington
Adams
Clear Denver Creek Jefferson Summit
Eagle
Garfield
Sedgwick
Broomfield
Conejos
Alamosa
Costilla Costilla
LegendLegend Mortality rate 100,000 per 100,000 Mortality rate per 73.8-143.0
73.8-143.0 143.1 - 160.8 143.1 -160.9 160.8 - 179.1 160.9 - 179.1
Baca
Las Animas Las Animas
Baca
179.2 - 197.5
179.2 - 197.5 197.6 - 269.7 197.6 269.7 County -Boundaries County Boundaries
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SOCIAL RISK
EVELINN BORRAYO, PHD
CATHY BRADLEY, PHD
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Interestingly, the idea of “exposure” goes beyond chemicals and radiation in the air and soil around you. There are social exposures too, and not just to obvious things like secondhand smoke. The term “social risk” describes the risks associated with the human systems around us. Then, these social risks are associated with physical risks that increase the chance of developing cancer. Here’s what we mean: A 2015 study of almost 9,000 people showed that when folks have at least three of the social risk factors of low family income, low education level, minority race, and single-living status, the risk of death from cancer was almost double that of people with fewer social risk factors. And with high social risk, the chance of dying from tobacco-related cancers was 2.6 times that of lower-risk populations. That’s right, we’re talking about race, education, socioeconomics, and their association with risk factors like smoking, obesity, and alcohol use. And social risk along with its associated physical risk factors does go a long way toward explaining the disparities in cancer diagnosis rates across Colorado counties. “The social determinants of cancer tend to cluster with geography,” says Evelinn Borrayo, PhD, CU Cancer
Center Associate Director for Community Outreach and Engagement. The median household income in Mesa County is $52k, while the median household income in Summit County is $74k. Both obesity and smoking are higher in Mesa County than in Summit County. And while Summit has more sun-associated cancers, they are far outweighed by cancers of the lung, breast, liver, pancreas, bladder, and colon that are associated with social risks in Mesa and Kiowa Counties. In fact, it’s not just a hodge-podge of counties that happen to be richer or poorer and have higher or lower cancer diagnosis rates. Instead, there’s a great divide in Colorado cancer risk in the form of, well, the Great Divide. “Cancer maps show that rural areas of Colorado’s Eastern Plains, Western Slope, and far south have rates of cancer incidence and outcomes similar to those in Appalachia. On the other hand, the Front Range and mountain communities along the I70 corridor have cancer outcomes far better than national averages,” says Cathy Bradley, PhD, CU Cancer Center Deputy Director. Rural Colorado is higher in social risk and it’s also higher in cancer diagnosis rates. This goes a long way in explaining what Bradley calls “cancer incidence,” but what’s to blame for the second piece of the puzzle, namely cancer outcomes?
ACCESS TO SCREENING AND CARE The earlier a cancer is detected, the better the chance of survival. There are two major checkpoints for this early detection: Colorectal, breast, and lung cancer screening can help identify and treat cancer even before it causes symptoms (sometimes even before it is technically “cancer”), and easy access to care makes it more likely to pick up cancer during a routine physical or to identify symptomatic cancers before they metastasize to become widespread, more dangerous stage IV disease. “There are eleven counties without a hospital and two counties without a doctor,” Bradley says. “In Colorado, the overall lung cancer five-year survival rate is 70 percent but only 55 percent in rural areas with less access to care.” “A lot of it is just access and availability of resources,” says Borrayo. “In the Front Range, you have clinics where you can get a mammogram, a colonoscopy, etc. Or you can get symptoms checked out right away. In more rural areas, even if you’re not in the poverty rate, access is more difficult. Whatever creates lack of access also creates higher cancer mortality rates.” Lack of access to prevention, early detection, and treatment in rural areas is so dangerous that the Centers for Disease Control now list “rurality” as a cancer risk factor, nationwide. All said, does where you live decide whether you develop and die from cancer? Not really. At least, not directly. As far as we know, there’s nothing in the soil or water or air in high-cancer counties of Colorado. But indirectly, where you live very much influences your cancer risk. Through social risk and lack of access to care, people in areas of the state with fewer resources are more likely to be diagnosed with and die from cancer.
SUMMIT COUNTY 241 CANCER CASES 100,000 PEOPLE DE ATH 30%RATE
MESA COUNTY 410 CANCER CASES 100,000 PEOPLE DE ATH 37%RATE
KIOWA COUNTY 487 CANCER CASES 100,000 PEOPLE DE ATH 54%RATE
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S U P P O R T E R
F CUS
‘Miracle Patient’ MAKES NEW RESEARCH POSSIBLE BY G a rt h S u nde m As a founding partner and lead investment strategist of the wealth management firm, Sterling Partners, it seemed like Debbie Silversmith never had time for things like a physical. It wasn’t until her husband, Don, “bugged her into getting a scan,” as he says, that Debbie finally made an appointment. “That’s when they found a golf-ball-sized tumor in my lung,” Debbie says. “They said forget about everything else, we have to do something about this tumor!” In April 2000, Debbie had the tumor and a lobe of her lung surgically removed, and in August of that year, she climbed Quandry Peak. Just in case, she would follow up periodically with internationally renowned lung cancer expert and CU Cancer Center Founding Director, Paul Bunn, Jr., MD. For 12 years, it seemed like Debbie’s cancer was in the rearview mirror. Then in 2012, Debbie had surgery for an unrelated condition. After the surgery, “I was young and thought I was in great shape, but my recuperation was going miserably. I was doing all these exercises and other people were advancing better than I was,” Debbie says. What was the problem? The problem, it turned out, was that her cancer was back. Doctors at UCH found a mass on her liver and another smaller one on her spine. At that point, it was no longer “lung cancer” and Dr. Bunn worked with Debbie to transition her care to GI specialist, Wells Messersmith, MD, Associate Director for Translational Research at CU Cancer Center and Head of the Division of Medical Oncology at the CU School of Medicine. “One of the great things about the oncology program here is that it’s very collaborative with other oncology centers around the country,” says Don. “Messersmith suggested we get in touch with an expert at Dana Farber and while we were in Boston, we conferenced with Wells and developed our treatment plan. We looked around at where there’s expertise in the recommended procedures and came back to University of Colorado Hospital. It was terrific because all Debbie’s treatment could be done in Denver.” Debbie’s lung cancer was a carcinoid tumor, which is a rare, slowgrowing cancer that arises from a special kind of hormone-releasing cell called neuroendocrine cells. The lungs are certainly not the only part of the body that has neuroendocrine cells. In fact, they are found on most organs of the body, especially those of the gastrointestinal tract. “My lung cancer was related to my liver cancer,” Debbie says. “They can only imagine that after years and years of the lung cancer growing slowly before surgery, it metastasized to the liver.” Under Messersmith’s supervision, Debbie had radioactive pellets implanted in her liver, followed by two years of oral chemotherapy. Interestingly, the oral chemotherapy Debbie took had never been approved to treat liver cancer, but Messersmith and his team knew of research showing its effectiveness against neuroendocrine tumors, particularly in the liver. Not only did Dr. Messersmith provide innovative, research-based treatment, but, “He went out of his way to make sure the drug was picked up by our insurance,” Debbie says. “I bet that’s not something they taught him in med school!” Neuroendocrine tumors are slow-growing and treatable, but most eventually return.
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D O N AND DEBBI E SI LVERSMI TH “I’m not expected to be cured,” Debbie says. “But now it’s been since the summer of 2015 that I’ve had chemo or radiation and everything looks good. Dr. Messersmith calls me his miracle.” After the care Debbie received from Dr. Messersmith and the rest of the UCHealth and CU Cancer Center teams, Debbie and Don asked Dr. Messersmith what they could do for him. Cancer research requires stateof-the-art infrastructure and high-tech instruments. But these tools are nothing without creative and motivated people to put them to good use. And that’s what Dr. Messersmith needed. With support from Don and Debbie Silversmith, Messersmith and his team were able to recruit Lauren Fishbein, MD, PhD, from University of Pennsylvania to a faculty position splitting patient care at UCHealth University of Colorado Hospital, with research at CU Cancer Center. Not coincidentally, Dr. Fishbein studies neuroendocrine tumors. “The generous gift from the Silversmiths has allowed us to expand on the spectrum of neuroendocrine tumors we study. In fact, based on data generated with support of their gift, the lab was able to obtain a pilot grant focusing on a particular type of lung neuroendocrine tumor,” Fishbein says. As for Debbie, she’s not letting her cancer slow her down. She and Don just got back from a bike trip to Ireland. “We met in Galway, on the western coast, and went both north and south from there, and the landscape was staggering – along what they call the Wild Atlantic Way. It was windy and rainy, but we were very prepared for it. What really sticks with me is the topography, between ocean and these craggy rocks and mountains. It was just spectacular, some of the most gorgeous scenery we’ve ever seen.”
“Dr. Messersmith calls me his miracle.” Dr. Messersmith’s miracle patient is going strong. And with the Silversmith’s support, future generations of patients in Colorado and beyond now have a better chance of earning the same title.
D O N O R
N E W S
Nancee and Paul Pronsati help make Denver hub of research, treatment, and community for ALK-positive lung cancer
Dinner in White
If Nancee Pronsati had been diagnosed with
tickets in advance not knowing
stage IV ALK-positive lung cancer a decade ago,
where it will take place until the
her years of life expectancy would have been
location is released the day of
measured with fewer fingers than it takes to make
the event. It’s an unforgettable
a peace sign. But due to advances in genetically
evening, an awesome date night,
targeted therapies, many driven by research and
and a fun way to raise awareness
testing at CU Cancer Center, Nancee is 3.5 years
for cancer research! Stay tuned
out from diagnosis and doing well. In honor of
this spring for announcement of
November’s Lung Cancer Awareness month,
the 2020 date.
Following the Parisian “Diner en Blanc” theme, guests at CU Cancer Center’s annual Dinner in White purchase their
Nancee and her husband, Paul, are giving back to CU Cancer Center research programs that are developing the next generation of treatments against ALK-positive lung cancer.
Over the Edge with James DeGregori, PhD, to help the Cancer League of Color ado Maybe in early September, you looked up at the roof of the Hyatt Regency Denver and thought to yourself, “Hey, there’s James DeGregori, PhD, falling from the sky!” In fact, DeGregori wasn’t falling from the sky – the CU Cancer Center Deputy Director along with 192 other intrepid souls were rappelling 39 stories from the Hyatt roof in what is Cancer League of Colorado’s (CLC) most deathdefying fundraising event, Over the Edge. “The CLC has supported millions of dollars for cancer research in Colorado, including numerous grants to my lab. I’m absolutely terrified, but I did it anyway. Maybe it helped that PA UL A N D N A N C E E PR ON SAT I
I promised to pledge an extra $500 donation if I chickened out,”
“I was diagnosed when living in New York City and started treatment at Memorial Sloan
DeGregori says. Since its start in 1969, CLC
Kettering,” Nancee says. “But my thoracic
has raised over $16 Million dollars
oncologist there knew I was from Denver and
for cancer research and patient
encouraged me to come home for treatment due
care in the state of Colorado. Not
to the incredible researchers and doctors here.”
bad for an entirely volunteer-run
It’s the ferocity and passion of people like
organization!
Nancee and Paul Pronsati that will help to ensure that new treatments against the disease continue
JA M ES D EG R EG O R I , P H D , H ANDS- FREE O VER DENVER
to come from Colorado.
Get more CU Cancer Center news on our blog: www.coloradocancerblogs.org Sign up for our bimonthly newsletter, Colorado Cancer News.
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UNIVERSITY OF COLORADO
WINTER 2019 www.coloradocancercenter.org
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ANSCHUTZ MEDICAL CAMPUS 13001 EAST 17TH PLACE, MSF434 AURORA, CO 80045-0511 RETURN SERVICE REQUESTED
C3: Collaborating to Conquer Cancer Published twice a year by University of Colorado Anschutz Medical Campus for friends, members, and the community of the University of Colorado Cancer Center. (No research money has been used for this publication.) Editor: Garth Sundem | 303-724-6441 | garth.sundem@ucdenver.edu Contributing Writers: Taylor Abarca Design: Candice Peters | Design & Printing Services University of Colorado The CU Cancer Center Consortium Members UNIVERSITIES
Colorado State University University of Colorado Boulder University of Colorado Anschutz Medical Campus INSTI TUTIONS
UCHealth University of Colorado Hospital Children’s Hospital Colorado Denver Veterans Affairs Medical Center Visit us on the web: www.coloradocancercenter.org The CU Cancer Center is dedicated to equal opportunity and access in all aspects of employment and patient care.
T H E
M E S S A G E
Building Relationships While Testing New Treatments Clinical trials are the make-it-or-break-it tests that
years. Often, these relationships aren’t easy.
determine which new treatments become part of
Many patients on early-stage cancer clinical trials
the cancer-fighting toolkit. It can take decades
will not benefit from treatment and I know from
of lab work to reach a phase 1 trial and can cost
speaking with people in our CCTO that everyone
hundreds of millions of dollars to run a phase 3 trial.
there has their own way of dealing with the end of
During this time, patients and their families hold out
a relationship. The thing is, while it’s not easy to
hope that a new drug could be the right drug.
work in the CCTO, without their work it wouldn’t
To call clinical trials high stakes is an understatement. We picture researchers, doctors,
many ideas for new treatments we have. Without
patients, and drug companies all with so much on
the work of the people in our CCTO, we’d be stuck.
the line. But at institutions like CU Cancer Center
FROM THE DIRECTOR RICHARD SCHULICK, MD, MBA DIRECTOR, UNIVERSITY OF COLORADO CANCER CENTER CHAIR OF SURGERY, UNIVERSITY OF COLORADO SCHOOL OF MEDICINE
that run clinical trials, none of this would be possible
high stakes is an
The 140 or so people in our CCTO are the ones
understatement.”
making sure patients are in the right places at the right times for the right treatments and tests – the
So whether you’re a patient, a researcher,
ones double-checking that every i is dotted and
a doctor or anyone else in the cancer community,
t crossed on the right forms, and making sure all
take a minute to appreciate the people who make
the data stays organized.
clinical trials possible. Take a minute to thank the
with cancer patients and their families that can last
WWW.COLORADOCANCERCENTER.ORG
“To call clinical trials
without the Cancer Clinical Trials Office (CCTO).
Even more than that, they create relationships
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matter how many discoveries we make or how
people in our CCTO for their dedication and their compassion.