Chipping Away

You notice it right away: a white-noise symphony of refrigerators, freezers, incubators, shakers, mini-furnaces, centrifuges, and, most notably, massive servers. The low hum is the soundtrack to which scientists at the University of Colorado Cancer Center methodically attempt to unlock the secrets of a complex disease.

In a series of laboratory alcoves, each dedicated respectively to lung, breast, colon, and pancreatic cancers, M.D.s, Ph.D.s, and basic researchers wield pipettes, tubes, culture dishes, microscopes, and voluminous three-ring binders. In the so-called dry labs down the hall, a bioinformatics team—experts who store, organize, and analyze biological data—examines terabyte after terabyte of information about the gene sequencing of different tumors.

Just one building to the south, in a suite that lives beyond a set of positively pressured doorways, nearly every one of the Anschutz Cancer Pavilion’s 50 infusion bays is filled with a patient enduring the slow drip of chemotherapy. The sheer number of people in need of treatment on a recent Wednesday morning is overwhelming, but it shouldn’t be surprising. Cancer—not heart disease—is the number one killer of Coloradans.

Our state’s relatively high life expectancy, increasingly elderly population, and comparatively low obesity rates—three seemingly positive measurables—may actually be contributing factors in cancer’s continued victory over coronary artery disease as the Centennial State’s top cause of death. And Colorado’s cancer fighters, like thousands before them over thousands of years, are ramping up the war on what many have called an immortal disease.

For as complicated as cancer may seem, it can be described in one simple phrase: the uncontrolled growth of a cell. Cancer cells lack the regulation that tells normal cells to cease dividing; they also elude the signals that direct a cell to die. Of course, cancer’s indefatigable passage has also continued to (mostly) thwart human intervention. No matter what we’ve thrown at it over time—radical surgeries, vitamins, supertoxic chemotherapies, vaccines and other preventive measures, radiation—cancer has often found a way to thrive. It is sneaky and highly adaptable.

But those adjectives are just as apt for the surgeons, oncologists, hematologists, radiation oncologists, and clinical and lab researchers who spend their days—and nights and weekends—looking for ways to outfox an ancient disease that is still killing more than 500,000 Americans every year. With exacting skill and unrelenting passion, Colorado-based physicians are employing every known weapon in the arsenal—the newest incarnations in cancer surgery, chemotherapy, radiation, screening, and prevention—and, in many cases, pushing the field to the cutting edge, where a deeper understanding of the disease is yielding novel therapies.

8 Myths of Cancer

MISCONCEPTION: Tumor biopsies and/or surgical procedures always make cancer spread

TRUTH: The risk that surgery will cause a cancer to spread—or metastasize—to other parts of the body is extremely low.

MISCONCEPTION: For those who are in remission from cancer, a clear positron emission tomography (PET) scan or nonexistent tumor markers in the blood mean the cancer has been cured.

TRUTH: Cancer is a shifty and cunning disease; although scans and blood draws may come back negative, that doesn’t mean the cancer will never recur. It can lie in an undetectable state and then reappear with no warning.

MISCONCEPTION: All cancer drugs have terrible side effects.

TRUTH: Chemotherapy drugs frequently do have unpleasant side effects such as hair loss, nausea, and fatigue; however, not everyone responds the same way to every drug. Radiation therapy can cause fatigue, skin damage, and hair loss at the site of radiation, among other things. Newer targeted therapy drugs have some side effects—rashes, high blood pressure, wound-healing issues—but they are infrequent and often less dramatic than chemo or radiation.

MISCONCEPTION: A positive (or negative) attitude can affect cancer outcomes.

TRUTH: There is no convincing scientific data that suggests a person’s attitude is linked to how well they respond to cancer treatment.

MISCONCEPTION: Tight underwire bras can cause breast cancer by compressing the lymphatic system.

TRUTH: No scientific evidence has ever shown the type of bra or tightness with which someone wears one causes cancer.

MISCONCEPTION: There is a singular cure for cancer; we just haven’t found it yet.

TRUTH: There are more than 100 types of cancer, and doctors treat them all differently. In fact, new research suggests that even the same kind of cancer—say, of the colon—could be strikingly different from person to person, meaning the treatment for one disease could vary from person to person as well.

MISCONCEPTION: Cancer is a death sentence.

TRUTH: For many cancers—breast, prostate, thyroid, childhood acute lymphoblastic leukemia—the five-year survival rate exceeds 90 percent. The overall five-year survival rate for all cancers is about 66 percent.

MISCONCEPTION: Cell phones, power lines, and artificial sweeteners cause cancer.

TRUTH: There have been no studies positively linking cell phones, power lines, or the sweetener you put in your tea to cancer.

Life Lessons

Inspired to be a physician by a general practitioner and a surgeon he knew as a kid growing up in Cheyenne, Wyoming, Dr. Alan Feiner has been practicing hematology and oncology for more than 35 years—all of them spent at Rose Medical Center. The gray-haired, mustachioed doc has the gentle, good-natured affect of a pediatrician combined with a humble wisdom attained only after a protracted relationship with cancer. Feiner sees 15 to 20 patients a day—a scant number in comparison to many of his Rocky Mountain Cancer Center colleagues—because he so enjoys interacting with his patients that he can rarely cut an appointment short. Feiner’s relationships with patients; his fascination with biology; his varied intellectual interests; and his long career make his thoughts, below, on the murky world of cancer particularly salient—and incredibly illuminating.

What is a doctor? A doctor of law…a doctor of divinity…a doctor of philosophy…a doctor is a teacher. Ultimately our job, in addition to taking care of patients, is to teach them. So when a patient comes in scared and panicked, that’s what we should be about: education. I go out of my way to care about their understanding.

When I first started years ago, there was much less of an understanding of cancer and the treatments were toxic, nonspecific, and ineffective; it was horrible. We essentially just did what we could.

The science of what’s going on in oncology today is fascinating. The biology, the new developments, the novel treatments, the better understanding of the disease. This is the golden age of cancer knowledge.

Understanding the problems that exist inside the genotype that lead to malignancy leads to so-called targeted therapy. It’s exciting. Targeted therapy doesn’t work for everyone, and it’s probably overhyped and too expensive and all of that, but it is progress.

Only two to three percent of American cancer patients are ever enrolled in clinical trials. My excitement, while I do refer patients to clinical trials, comes instead from looking at a person’s individual characteristics and deciding what’s best for them. There are doctors who treat diseases and there are doctors who treat patients with diseases. We may need both, but I prefer to treat the people with the diseases.

If you say, “My fulfillment will only come by curing everyone,” you won’t last a day in hematology or oncology. The fulfillment comes in helping people at a time when maybe only you can help them.

Here’s what’s so fascinating about oncology: You sit there and ask yourself, What’s the most common tumor to metastasize to the brain? Then you answer: It’s lung cancer. Then another question: But why? Those patterns and pathways are intriguing.

The two most important pieces of medical equipment I own are my two ears.

How do I do what I do without burning out? I’m renewed by the people I work with. It takes a village to take care of one cancer patient and the other people—the doctors, nurses, dietitians, caseworkers—energize and strengthen me.

Finding a good oncologist or hematologist is tricky. Everyone’s got credentials, everyone’s got referrals. My advice: Go to a good hospital. Good people are usually surrounded by other good people.

People are afraid of death—but they are more scared of suffering.

I’ve recently been studying neuroscience, philosophy, religion, ethics; studying outside of oncology and hematology has been helpful for me and given me different perspectives I can use in my practice.

Oncologists tend to be optimists—we may be guilty of overhyping things (like the new targeted therapy drugs), but that keeps the energy flowing, and that’s important.

Some people get better because of us; some people get better in spite of us; and some people just get better.

Drug Dealmakers

In a little more than two years, two of Colorado’s most visible public servants—Senator Michael Bennet and Governor John Hickenlooper—have been in the spotlight for co-sponsoring or signing legislation that aims to cut through the bureaucratic mess that comes with approving novel or lifesaving drugs, many of them for cancer:

Advancing Breakthrough Therapies for Patients Act:

Part of the 2012 Food and Drug Administration Safety and Innovation Act (FDASIA), Bennet’s provision provides for a new designation that pushes the FDA to expedite the development and review of drugs that intend to treat serious or life-threatening conditions and have shown preliminary clinical evidence that they are better than existing therapies. The FDA must review all requests for breakthrough therapy designation within 60 days of receipt.

Right to Try Law:

Colorado became the first state in the nation to pass a so-called “right to try” bill when Hickenlooper signed it into law in May 2014. The bill allows terminally ill patients to have access to unapproved, investigational drugs. Supporters say the red tape surrounding the FDA’s “compassionate use” clause is too onerous for those facing death. Detractors say the new law will have zero effect as it simply reiterates what federal policy already allows.

Right Place, Right Time

It started with a cough, a dry hack that 41-year-old Susan Nunn really only noticed when she was out for a run, one of her near-obsessive pastimes. The pretty brunette with dark brown eyes attributed the rattle in her chest to smoke in the air from the summer 2012 wildfires raging in Colorado Springs, less than 20 miles from her home in Monument. But after a few months, the coughing worsened enough to affect Nunn’s exercise routine, so she went to the local urgent care center. One week later—after X-rays, a CT scan, and a biopsy—the married mother of two was diagnosed with Stage 4 metastatic lung cancer.

For Nunn and her husband, Tyson, the statistics associated with her diagnosis were nothing short of terrifying. Although Nunn had never been a smoker, she would have to be extraordinarily lucky to fall into the 3.9 percent of late-stage lung cancer patients who live five more years. In fact, she would be fortunate to see her next birthday: 50 percent of people diagnosed with lung cancer die within one year. Nunn, looking at Tyson and thinking of her kids, immediately decided that wasn’t going to be her reality. Dr. Ross Camidge, an innovative University of Colorado Cancer Center medical oncologist, gave her hope it wouldn’t be.

Researchers have long flirted with the idea that genetics play a powerful role in cancer, but only in the past eight or nine years has science been able to understand the biology of cancer cells well enough to begin to affect change for patients. Throughout much of cancer’s history, scientists and doctors believed cancers were mostly homogeneous, meaning all colon cancer was the same, all ovarian cancer was the same, and all skin cancer was the same. “In that very recent past,” says Camidge, who came to CU eight years ago from Britain looking for a research center that would allow him to work outside the proverbial research box, “we’d vaguely open the cupboard and give the blue pills to someone with breast cancer and the red pills to someone with lung cancer.” And although those medicines, especially through the ’90s and early 2000s, had some success, there was little explanation for why one patient responded to chemo and another didn’t.

The answer, researchers like Camidge are now learning, is that tumors—even tumors of the same type of cancer—are not uniform at all. They are fundamentally different because chromosomes of the cancer can be as unique as what differentiates one person from another. “There can be hundreds of subtypes of every cancer,” Camidge says, “and we may need a very personal treatment regimen for each one of them. That could be a type of chemo, or it could be something else.”

That customized therapy is made possible, in part, by a relatively recent revolution in technology. “Technology has changed to allow us to look for multiple molecular abnormalities,” Camidge says, “for a noncumulative increase in the price.” As recently as five or six years ago, gene testing was cost-prohibitive—$1,000 for a single gene test, whereas now the price is closer to $5,000 to test 400 genes (genes are now tested in large batches, but the math works out to about $12.50 per gene). That drop in price is allowing researchers to molecularly profile a person’s tumor to find out if a genetic mutation is driving the cancer and, hopefully, match it to a drug that specifically targets the abnormality. In Nunn’s case, her lung cancer tested as ALK-positive. ALK stands for anaplastic lymphoma kinase, a normally occurring gene in human cells. But inside Nunn’s petite frame, an unexplained mutation in that same gene was spurring an unruly replication of cells. Knowing Nunn had the ALK mutation, Camidge put her on a then newly FDA-approved prescription drug called crizotinib, a targeted therapy for ALK-positive, advanced-stage lung cancer that had been effective in 50 to 60 percent of patients in clinical trials.

Nunn’s cancer began to shrink dramatically. “You wouldn’t have believed the difference in my first PET scan and the one after going on crizotinib,” Nunn says. “I was taking a pill twice a day—with very minimal side effects—and I felt so much better within one week.”

If Nunn had come down with her cough in 2006 instead of mid-2012, there would have been no magical acronym—much less a drug to treat it. The ALK-positive mutation, which appears in about five percent of lung cancer patients, wasn’t discovered until 2007. In fact, in early 2004, only one major mutation, KRAS, had been described in lung cancer; by mid-2014, researchers had isolated more than 20 others (see chart above), many of which can be treated. As more and more of these mutations have been found in the lab, pharmaceutical companies have, partly because of the economic incentives, begun to quickly develop drugs to counteract them. The FDA, likewise, has been fast-tracking many of these targeted therapy drugs.

That progress will need to continue because, as happens with many targeted therapy drugs, Nunn’s cancer began to flourish again after only three months on crizotinib. “Her cancer, which was naughtier than most, mutated again,” Camidge says. “We saw evolution happening.” After radiation and chemo failed to stop the cancer’s growth and spread—five brain tumors, which required neurosurgery, were found on a scan—Camidge knew Nunn needed second-generation ALK-positive targeted therapy that would be better able to control the cancer, especially in her brain. To do that, he had to get Nunn qualified for a clinical trial of AP26113, a drug from Ariad Pharmaceuticals. “We’re continuing to find out why and how a cancer can become resistant to a drug like crizotinib,” Camidge says. For now, though, Nunn’s cancer is responding to AP26113. “I take six pills every night before I go to bed,” Nunn says, explaining her only side effect has been some mild nausea, “and since going on the drug, all the cancer has melted away. I run, I hike, I feel like a totally normal person.”

Camidge agrees that Nunn is normal, but he means something entirely different when he says it. “Susan is not exceptional,” says Camidge. “She’s representative of where an understanding of biology, molecular profiling, access to clinical trials, and pushing clinical care can get you. It may be within our power to make cancer a chronic disease—much like we’ve done with HIV—in the near future.”

This month marks the two-year anniversary of Nunn’s diagnosis. She has been on AP26113 for 14 months. “The longest anyone has been successful on AP26113 is two years,” Nunn says, “so I don’t know how long it’s going to work. It could stop working tomorrow or it could work for me forever. What I do know is that I’m here because of research. I just hope I can stay one step behind big-brained people like Dr. Camidge.”

Converging Factors

Fifty-four-year-old Karen Wehling knew she should see a doctor for her symptoms, but her sore rear end seemed inconsequential compared to her husband’s pain. Paul was in the middle of treatment for cancer of the larynx, and Karen knew she needed to focus on him. After all, some discomfort when she sat down and occasional blood in the toilet probably just meant a case of hemorrhoids. She could wait.

When Paul’s treatment ended in January 2011, Karen thought for a moment about scheduling a doctor’s appointment for herself—but when Paul died unexpectedly from complications associated with his cancer two weeks later, that call fell far down on the priority list. “I was devastated,” Karen says. “It was four months before I told myself I needed to get out of bed and get my health taken care of.” In June 2011, Karen went in for a colonoscopy thinking she might need a minimally invasive procedure to treat her hemorrhoids, but when the test results came back, they told a different story: Karen had Stage 4 colorectal cancer.

Karen had a choice to make. “I already wasn’t happy about going on without my husband,” she says, “and then I found out about the cancer. I had to decide if I was going to fight, and if I was, I needed to decide I wasn’t going to be sad all the time.” And so Karen’s journey began.

On a recommendation from Paul’s doctors, Karen ended up in Dr. Wells Messersmith’s office at the Anschutz Cancer Pavilion. A medical oncologist, Messersmith specializes in gastrointestinal cancers—both in a clinical and research setting. The doctor did a biopsy on Karen’s tumor—testing for KRAS and BRAF mutations—and then put her on chemo and radiation therapy. But Messersmith knew, even with chemo and radiation, Karen’s prognosis was not good. Patients with Stage 4 rectal cancer have a six percent five-year survival rate. He needed to try something else.

“Although most centers were not yet testing for the BRAF mutation in 2011,” Messersmith says, “we had the ability to do so—and I was encouraged when I found out that Karen had a BRAF mutation.” Encouraged, because the 44-year-old physician knew he could get Karen into a clinical trial for a targeted therapy drug combination that had proven successful in some patients who had melanoma with a BRAF mutation. Messersmith took Karen off chemo and put her on trametinib and dabrafenib, a combination of BRAF-inhibitor drugs. Karen was on the duo of drugs for just a few months before it became apparent the targeted therapies weren’t working. “Colon cancer can have a BRAF mutation and melanoma can have a BRAF mutation, so you’d think a BRAF inhibitor should work in both diseases,” Messersmith says. “It turns out it doesn’t work at all in colon cancers.”

For Messersmith, it was another learning experience in the uncharted era of molecular profiling; for Karen, it meant another round of chemo and radiation. It also meant trying to find support when the one person she had always looked to was no longer there. “My kids were great, but I didn’t want them to have to worry about their mother dying so soon after losing their father,” Karen says. “I asked Dr. Messersmith if there was a colorectal cancer support group at University Hospital. I was surprised when he said no. He gave me the name of a Facebook group instead.”

“Colontown,” a private Facebook group for colorectal cancer patients, became Karen’s bedrock of support. “It makes sense in this electronic world,” Karen says. “It’s a good place to support others and have them support you. Let’s face it: You have a lot of gastrointestinal issues with rectal cancer, and you can talk to these people about anything—including poop. Your kids and friends don’t want to talk about that.” Through Colontown and a typical support group she helped ignite at University Hospital, Karen found not only support but also friends who ultimately went to each other’s doctor’s appointments and treatments. “Having people around you who ‘get it’ makes the cancer treatments much more palatable,” she says.

A year after her diagnosis, and after chemo and radiation had shrunken her tumors, Messersmith and a multidisciplinary team of surgical oncologists, radiation oncologists, endoscopists, and specialized pathologists—a perk of being at a large academic institution where specialists can gather en masse—decided surgery was Karen’s next best treatment option. In August 2012, surgeons removed Karen’s rectum as well as a tumor in her adrenal gland and two unrelated masses in her liver—and she’s been cancer-free ever since. The now-57-year-old knows she’s living on borrowed time, a blessing that has allowed her to find new reasons to live, particularly her grandchildren and other cancer patients who need her support. She, of course, credits Messersmith with saving her life—especially because she knows her grief often rendered her incapable of making careful decisions about her health.
Although medically complicated, Messersmith sees Karen’s case as one imbued with cancer’s newest truths. “Yes, Karen has cancer in an age when we’re using molecular profiling to our advantage, but she and I learned together that targeted therapy doesn’t always work,” Messersmith says. “We also learned how social media can impact cancer treatment and cancer patients in a positive way—something Karen wouldn’t have had access to 10 years ago. So, genetics and social media—two modern-day revolutions—are colliding in cancer right now.”

Facebook Is My Research Assistant?

While online groups have provided unquantifiable emotional support to cancer patients like Karen Wehling, many physicians and researchers are just beginning to see the possible advantages of social media sites such as Facebook and Twitter on the medical provider side. Although there are privacy issues to consider, the upsides are difficult to deny. “Some people have thrown out the idea of crowd-sourcing cancer research,” Dr. Wells Messersmith says. “Today, patients can get their genes sequenced—that price has dropped from $3 million and six months of time to $10,000 and six hours of wait time—and they could upload their DNA sequences and provide other clinical information. If hundreds and hundreds of people do that, it could be a huge tool for researchers.”

Bespoke Medicine

In The Emperor of All Maladies, the Pulitzer Prize–winning biography of cancer by Dr. Siddhartha Mukherjee, the oncologist turned author explains in a back-of-the-book Q&A: “Every era casts cancer in its own image, and this happens to be the era of genetics. Therefore, we use genetics to understand cancer.” Reading this line out of context, one might assume Mukherjee lacks faith in the newest frontier in cancer research; however, that’s not the case. He’s just postulating genetics might not be the final frontier.

He may be right, but using genetics to fight the replication of cancer cells is a significant leap. It may also be a huge step for treating other illnesses—some of which science may not yet know have a genetic component.

At least, that’s the reasoning behind the new $63 million Center for Personalized Medicine and Biomedical Informatics, an effort supported by University of Colorado Health, the University of Colorado School of Medicine, and Children’s Hospital Colorado. Over the next half-decade, those entities will add clinicians, genetic counselors, researchers, a DNA bank, and analytics tools, most of which will be housed on the Anschutz Medical Campus.

“Cancer is pioneering the field of genetics,” says Dr. Wells Messersmith, a medical oncologist. “But the question is, in a few years, could we be testing for thousands of genes, not just 400?” This center, says Messersmith, will keep Colorado in the upper echelon of cancer centers that are generating new knowledge. And with the data that should be collected in the first years—not just about cancer, but about the genetic foundations of other diseases—organizers hope to be able to predict and prevent disease, identify new treatments, and, using the DNA bank, search for gene sequences and biomarkers that point to weaknesses in modern diseases.

Hot Shot

In the nerdy world of oncology research, calling anything “sexy” might seem a bit sardonic. But if anything has been getting cancer docs excited over the past five to 10 years, it’s the possibility of vaccine therapy. Unlike preventive cancer vaccines—like those for human papilloma and hepatitis B viruses, which can cause cancer—treatment vaccines are a type of immunotherapy that boosts the body’s inherent ability to fight a disease it already has. “Although the idea for vaccine therapy has been around for a long time,” says Dr. Barish Edil, a complex general surgical oncologist and cancer vaccine researcher at University of Colorado Hospital, “only recently has immunotherapy gotten to be a hot topic, one that really does have serious promise.”

That newly harnessed potential is especially compelling for Edil’s pancreatic cancer patients. Cancer of the pancreas is a particularly fatal disease—five-year overall survival rates range from one to 14 percent based on the stage of the cancer—because it’s difficult to detect early and its location makes it challenging to treat. An operation known as a Whipple procedure (which, among other things, removes the head of the pancreas, where most tumors occur) is the best hope for a cure for a patient with pancreatic cancer; however, only about 20 percent of pancreatic cancer is caught early enough for surgery to be an option. Even with surgery, cancer of the pancreas has a high recurrence rate, and only 30 percent of patients who receive surgery will live to see five years. “As a surgeon, I realized I really wasn’t helping my patients enough,” Edil says. “That’s why I’m passionate about the vaccine we’re working on at CU.”

Although the vaccine is still in the early stages of research, Edil and his colleagues expect to patent the drug and move it into clinical trials in the next 12 to 24 months. When it reaches patients, Edil says the IV-delivered vaccine’s mission is to work in concert with a laparoscopic Whipple procedure (something Edil helped perfect) and assist the body’s immune system in sealing up gaps in its defenses and annihilating microscopic disease floating in the bloodstream that can cause recurrence or metastasis. Edil says the particular immune system “check point” his vaccine targets is unique in the world of immunotherapy. “We really believe that treatment vaccines like this one,” Edil says, “can be a new treatment arm, a true therapeutic option, for cancer.”

Screening

Red Flag Warning

Finding cancer before it causes symptoms is not a new idea (see the mammogram and the Pap smear); however, as science matures, the way we detect disease—either in healthy people or in those who may be in remission and at risk for recurrence—is ever-evolving. It’s also controversial. Screening tests can provide false positives that often lead to unnecessary treatment or false negatives that may allow disease to progress untreated. Even so, early discovery of cancer is universally recognized as the best way to fight the disease, and some of Colorado’s researchers are working to develop the next generation of tests.

The Test: Bladder cancer urine test

The Researcher: Dr. Dan Theodorescu, director of the University of Colorado Cancer Center

Why We Need It: More than 65,000 Americans will be diagnosed with transitional cell carcinoma bladder cancer in 2014. Although this type of bladder cancer has a high five-year survival rate when caught early (as high as 98 percent), bladder cancer patients are at a high risk for recurrence. That recurrence risk means patients must undergo frequent and costly follow-up exams at the doctor’s office—often for many years. If Theodorescu’s at-home urine test can mimic—or exceed—the accuracy of in-office exams, patients could not only avoid taking time off work or driving far distances to see the doc in person, but they could also help in reducing what is reportedly the most expensive malignancy to treat from diagnosis to death.

How It Would Work: Bladder cancer patients would get the tests—kits with sterile urine-capture tubes and prestamped envelopes—from their treating physicians. At a specified time, patients would take the test and send in their samples. If certain biomarkers in the urine suggest a recurrence, a patient would receive a phone message telling him to schedule an appointment with his doctor for further testing.

The Downside: Similar tests have been on the market for a while, but they have specificity and/or sensitivity flaws that, according to Theodorescu, render them mostly ineffective. Theodorescu’s test will employ a multigene, multiprotein panel that uses complementary approaches and biomarkers to improve upon the specificity and sensitivity of currently available detection technology.

The Test: Low-dose CT scan with blood test in those at high risk for lung cancer

The Researcher: Dr. James Jett, professor of medicine, division of oncology, National Jewish Health

Why We Need It: Lung cancer is the leading cause of cancer death, and at least 80 percent of those deaths result from smoking. In 2011, results from the National Institutes of Health’s National Lung Screening Trial (NLST) showed that participants in the trial who received a low-dose CT scan screening had a 20 percent lower risk of dying from lung cancer than those who received a standard chest X-ray. Jett’s study expands upon the NLST by adding a blood test to the CT scan to see if biomarkers can further help detect early-stage cancer, which in many cases can be cured.

How It Works: Participants who qualify for the trial* get a low-dose CT scan and a blood draw. The scan looks for visual signs of lung cancer while the blood test investigates whether the participant is positive for seven autoantibodies against cancer antigens. If the blood test is positive, the participant has a fivefold higher risk of developing cancer. (If the CT scan or the blood test is positive, Jett makes recommendations for participants to see a physician, but getting that treatment is up to the individual.) The trial follows up with all participants for two years.
The Downsides: CT scans can pick up 95 percent of all lung cancers, but they can also pick up noncancerous lung nodules. These nodules may require follow-up procedures to make sure they are benign. There is also a very low risk of radiation-induced cancer from the screening test. And lastly, blood tests are also susceptible to false positives and negatives.

*To qualify for the trial, a participant must be between 50 and 75 years old and have a 20 pack-year history of smoking; he or she can be a current or former smoker (but cannot have stopped smoking for longer than 10 years). To get more info, call 303-398-1921.

Risky Business

Bring up the Big C at a dinner party and everyone will have something to add to the conversation. That’s because cancer has affected almost all of us. But what if the story you could tell feels just a little too chilling to bring up over a meal? What if it seems like cancer is hunting your family members down one by one?

The genetics of inherited cancer have come a long way since 1872, when a Brazilian ophthalmologist noticed that a rare eye cancer seemed to run in a particular family. But more than 140 years later, science is still determining how, why, and what we inherit from our families as it relates to cancer. Fortunately for those of us who live in Colorado, that science has been revealing itself in fits and starts since the mid-1990s at the University of Colorado Cancer Center’s Hereditary Cancer Clinic, where a team of doctors and genetic counselors helps guide patients with above-average risks for cancer through education, early screening, risk assessment, and genetic testing.

“Most people’s cancer risk is lower than they think,” says Lisen Axell, a genetic counselor at CU’s Hereditary Cancer Clinic. “Only about 10 percent of cancers are considered inherited.” Of course that doesn’t mean you should ignore the fact that certain kinds of cancers run in your family. “If you are a 33-year-old woman with no history of cancer but you have two paternal aunts who both got breast cancer in their 40s or early 50s,” Axell says, “you might consider genetic testing for them and possibly yourself.” Axell chooses that hypothetical patient because inherited mutant genes—BRCA1 and BRCA2, discovered in the mid-’90s—were shown to increase a woman’s risk of breast and ovarian cancer. And other cancers have been shown to be inherited as well, including colon, brain, adrenal, endometrial, stomach, kidney, and prostate.

Axell stresses that people come to the clinic for many reasons. Some patients already have cancer and want to know if their kids have a higher risk for getting the disease. Others come to do a cancer risk assessment, which doesn’t involve any blood work whatsoever. She also says it’s important for people to understand that even if they have a genetic marker for a certain type of cancer, it doesn’t mean they need dramatic surgery à la Angelina Jolie. “We help people understand their options,” she says. “And there are multiple choices in most cases.”

Artful Explanations

Dr. Charles Leonard says he’s a failed creative writer cum radiation oncologist, but he has a way with words when speaking about radiotherapy. “The manner in which physics, biology, and technology are applied to patient care,” he says, “is what’s compelling about this type of oncology.” His passion is on display at Rocky Mountain Cancer Centers, where he treats patients every day. But it’s his ability to distill the complicated world of radiation into digestible nuggets of information that makes him an invaluable resource for cancer patients.

“The most pressing problem in radiation therapy today is knowing when and—maybe more important—when not to use it. A big question right now is: Are we overtreating? There are some cases of early-stage noninvasive breast cancer that we routinely treated in the past that I think we’re gradually realizing we don’t have to treat with radiation. I believe physicians should be measured by whom they don’t treat as much as by whom they do.”

“We’ve had a number of innovations and advances in our treatments in the past 15 years. Things like image-guided radiation therapy [the use of frequent imaging during therapy to improve precision] and intensity-modulated radiation therapy [therapy that uses tiny beam-shaping devices to deliver varying intensities of radiation] now allow us to be more precise and adjust the intensity and shape of the beams. Because of this, we’ve been able to reduce the toxicity of radiation therapy, which really had to do with our inability to avoid normal tissues.”

“Emerging tests that look at the genetic makeup of cancers could help us determine which tumors are going to respond to which therapies. Radiation will be a part of cancer treatment for the foreseeable future, but genomic testing may help us determine more effective and efficient ways to use it. I think we’re on the cusp of serious progress.”

“This is a technology-driven practice, but something we need to look at is, Is newer always better? We’ve been doing research that looks at three-dimensional conformal radiation therapy versus intensity-modulated radiation therapy. The latter is the newer, hipper, more expensive treatment, but is it better for every cancer? Because of the push to make health care more cost-effective, it’s worth knowing the answers to questions like this.”

One More Last Chance

Jeff and Linda Lambertson say they should’ve noticed that their two-and-a-half-year-old daughter Katie was lethargic and sleeping restlessly. Maybe they could’ve noticed she was a little pale and bruising easily. But hindsight, as they say, is always clearer. Instead, the Danville, California–based parents of three daughters didn’t know anything was wrong until Katie threw up after dinner one night. “Honestly, we took her to the pediatrician the next morning,” Jeff says, “because we had a nice weekend coming up that we were looking forward to.” He laughs and says in a soft, loving tone, “If only we’d known what was coming.”

The family’s pediatrician immediately latched onto the little girl’s pallor and bevy of contusions and ordered a blood test. When the results came back the following morning, the pediatrician sent the Lambertsons to a nearby hospital where doctors told them Katie had cancer and suggested an immediate medevac transfer to Children’s Hospital Oakland. A normal white blood cell count for a child is between 5,000 and 10,000 per microliter; Katie’s was 750,000. The Lambertsons’ tow-headed toddler had full-blown acute lymphocytic leukemia (ALL). At Children’s Hospital Oakland, Katie had to get blood transfusions just so doctors could do necessary procedures. “They told us we might lose her in the first 24 hours,” Jeff says.

Katie made it through the night, but the Lambertsons’ bad-news-laden journey had just begun. Doctors explained that Katie had a rare form of the cancer called T-cell ALL, a more aggressive, less-well-understood subtype that affects only about 15 percent of ALL patients. She would need chemo, and quickly.

An initial regimen of chemo usually puts pediatric patients into a temporary state of remission. But not Katie. After 30 days, her parents moved her to Lucile Packard Children’s Hospital at Stanford, where doctors were standing by to tackle Katie’s unruly form of the disease. After more chemo, doctors got the tot into a tentative medical remission and then recommended a bone marrow transplant as the only way to save Katie’s life. Her siblings were not matches, and although a donor was found, the match was not perfect. The Lambertsons and Katie’s doctors decided it would have to be good enough: Katie couldn’t wait. Five months after her diagnosis, Katie underwent total body irradiation to kill her immune system and then went through the transplant. It failed 100 days later. “We were at the end,” Jeff says. “She couldn’t get another transplant and there was nothing left doctors there could do.”

The Lambertsons decided that wasn’t acceptable. Even as they were hoping the transplant would work, they had been researching for the worst-case scenario. They found a clinical trial for T-cell ALL patients for a drug called forodesine, manufactured by BioCryst Pharmaceuticals. But there were obstacles: The trial had not yet been fully opened to pediatric cases; Katie had to be very sick, but not too sick; and few hospitals would even participate in what many considered experimentation on kids. “We moved heaven and earth to get her into the trial with BioCryst,” Jeff says, “but until the trial organizers suggested Dr. Lia Gore at Children’s Hospital Colorado’s Experimental Therapeutics Program, we didn’t know how we were going to get Katie the only drug we thought might work.”

Like almost every family that shows up to Gore’s clinic, the Lambertsons had been told their child was going to die. And like almost every parent Gore sees, Jeff and Linda needed to be absolutely sure they had exhausted every possibility to save their child. Gore founded the Experimental Therapeutics Program in 2003 to be the place families like the Lambertsons could come to. “It’s a privilege to take a family through this journey,” says Gore, whose vision it was to create a center where new treatments for kids with cancer could be tested and developed, “and how we do that is the ultimate challenge for me. Every day something comes up that wasn’t anticipated, so it’s really about how we move forward with each family and how we learn along the way to make it better for the next family.”

Ten months after her diagnosis and a few months after her transplant failed, Katie found herself on a clinical trial for forodesine under the care of Gore. There was little to no data on the drug in kids, and there was scant information on dosages, but Gore worked with BioCryst to get it right for Katie, the youngest patient ever to be given the drug.

That was nine years ago. After just two weeks on forodesine, Katie achieved full remission. After six months, she went off the drug completely—and has never relapsed. Today, Katie is a healthy 12-year-old who gets A’s and B’s in school, likes volleyball, and is learning to play golf. She has zero memory of the pain she experienced as a toddler, but she remembers Gore. Jeff and Linda remember Gore, too. “Dr. Gore is second to none,” Jeff says. “She and her team are with you 24 hours a day, and they made sure everything was always ready to go for Katie.”

All these years later, the Lambertsons are still hyperaware their daughter’s recovery was unlikely—that she is an outlier. Katie may be an anomaly in the grand pantheon of cancer statistics, but she is much like many of Gore’s other patients: kids who weren’t given a chance by anyone else and who, with the doctor’s help, beat astronomical odds. “There are a lot of kids whom we still can’t cure,” Gore says, “but childhood cancer is infinitely more curable now than 10 or 15 years ago. And that’s only because there are people like the Lambertsons who are willing to take a chance on experimental therapy.”

The Long Run

Surviving Childhood Cancer

In the ’60s, defeating pediatric leukemia was nearly unheard of—in fact, only five percent survived the onslaught of cells. Today, however, the cure rate frequently tips 90 percent. That upswing is one of modern medicine’s biggest success stories. But as pediatric cancer survival rates have continued to climb, a different kind of medicine has become necessary. “Kids weren’t living long enough back in the day for us to learn about the long-term side effects of cancer treatment,” explains Dr. Brian Greffe, medical director of the HOPE Survivorship Program at Children’s Hospital Colorado. “Now we know there are things that require follow-up care.”

Chemotherapy, radiation, surgery, and other newer treatments for childhood cancer can cause a host of long-term side effects: infertility, bone tissue death, heart and lung complications, cognitive impairment, endocrine issues, kidney damage, and secondary tumors. The problem is only about 20 percent of pediatric cancer survivors who are now adults get care to prevent, diagnose, or address problems that can arise years after treatment stops. Why? “We’re still educating doctors to look for symptoms and talk with patients about these issues,” Greffe says. “Plus, many patients have anxiety about going back to the doctor, or they simply don’t have a general practitioner once they get into their 20s or 30s.”

Greffe explains that even if a patient hasn’t had any complications, it’s a good idea to set up an appointment at the HOPE clinic—or at the adult-specific TACTIC clinic, an extension of HOPE located at University of Colorado Hospital. “The book of side effects is hundreds of pages long,” Greffe says, “but that means we know what to look for and we can often help before something goes wrong.”

Tech Upgrade

Over the past half-decade, robotic surgery has revolutionized the field of gynecologic oncology by bringing the advantages of minimally invasive procedures to more patients. Dr. Margrit
Juretzka, a gynecologic oncologist specializing in surgery at Saint Joseph Hospital, is particularly adept with the automaton. We asked her what it takes to excel at this surgery, who it affects, and why the advancement is so important.

5280: We’ve heard using the da Vinci robot is like a video game—were you good at Super Mario Bros.?
Juretzka: My parents didn’t let me play video games as a kid. I was totally disadvantaged. They almost ruined my career before
it started!

Why are you so good at it, then?
I’ve done a lot of these surgeries. And I think, just like for any surgery, it takes a certain amount of finesse.

What kinds of surgeries are you using the robot for?
We do lots of cancer staging surgeries (biopsies, lymph node dissection, explorations); we can also do radical hysterectomies and complex benign gynecological procedures.

Why has robotics become so important?
There’s been a big push for minimally invasive surgeries because there’s less blood loss, less pain, less infection, and a faster recovery. But not all patients are good candidates for traditional laparoscopy, which means we had to do big open surgeries instead. Obesity is a huge risk factor for uterine cancers, but laparoscopy in patients with high BMIs is difficult. With the robot, we can now do minimally invasive procedures on patients who have been shown to do poorly with open surgery.

Is minimally invasive surgery particularly good for cancer patients?
Yes. It’s better than open surgery in many cases because so many cancer patients have to go on chemo shortly after surgery. Chemo suppresses the immune system, which makes healing difficult. Our largest incision with the robot is 1.2 centimeters. An open surgery can have a large incision, which in chemo patients or those with high BMIs can lead to infections and months of difficult, painful healing.

Why do you like the robotic surgeries?
I enjoy the great visualization; I like how precise the machine is; and mostly I like seeing the dramatic difference it makes in my patients’ lives. They have so much less pain and a much better recovery. That’s important in patients who are already dealing with a cancer diagnosis.

Our Particular Susceptibility

Sunny days and high altitude are what make Colorado Colorado. Unfortunately, those things also make the Centennial State a hotbed for melanoma, a deadly form of skin cancer. National numbers suggest the lifetime risk of developing melanoma for Caucasians (who are most commonly affected) is 1 in 50; however, in Colorado that number creeps closer to 1 in 40. It’s fitting, then, that some of the most exciting research into this disease is being led by Dr. William Robinson, a Colorado native and University of Colorado School of Medicine alumnus, at Aurora’s Anschutz Medical Campus.

Although Robinson has been studying melanoma for decades, he says the past five years have been the most promising in terms of improving treatment for those with metastatic forms of the disease. Even more exciting was the gift Robinson and his team received in February: a $5 million endowment from an anonymous American donor who simply wanted to see melanoma cured. “This person and an advisory team did a worldwide search to find the place doing the best melanoma research,” Robinson says. “This person approved our proposal, and the money couldn’t have come at a better time.”

Robinson says he’s paraphrasing an old colleague when he says, “Melanoma is what gives cancer a bad name.” It’s dark humor, but the fact remains the disease has been notoriously resistant to chemo and radiation, and the five-year survival rates for late-stage malignant melanoma are abysmal.

With the $5 million donation, Robinson and his team are looking to improve upon recent successes in the field. In the past half-decade, researchers have determined about half of melanoma patients have a genetic mutation in their cancers called BRAF. About a year ago, the FDA approved a treatment—a signal transduction inhibitor—that shuts down the genetic mutation and halts the cancer. Scientists have also been developing another type of treatment called immunotherapy, which encourages a person’s own immune system to attack the melanoma. Both types of treatment, some of the most successful in the history of melanoma, elicit dramatic responses. Both types of treatments also have a time limit. BRAF inhibitors stall the cancer for only about 11 months; the immunotherapies last 18 months and then slowly fail.

Still, says Robinson, it’s progress, and a place to focus further research. Over the next few years, Robinson, four technicians, two bioinformatics specialists, and a lab of gene sequencing experts will undertake a project to molecularly profile more than 1,000 melanoma samples Robinson has been collecting in what is one of the world’s largest biorepositories for the skin cancer. “Before, we looked for one gene at a time,” Robinson says, “but with this project we’re going to do whole genome sequencing for each tumor, and we’re looking for mutations that we can target in melanoma patients.”

This approach is not novel; others are doing genetic sequencing of melanoma. What Robinson offered his gift-giver was the clinical data attached to each of his tissue-bank samples. “It’s important I know the tumor I’m sequencing came from a 35-year-old woman with a melanoma on her leg who had the BRAF mutation but did not respond well to targeted treatment,” Robinson says, “and whose melanoma spread to her liver. A slice of tumor and its genetic profile aren’t as helpful if I don’t know the patient’s story.”

The narrative Robinson has always known, however, is that melanoma rarely leads to a happy ending. Through his important research, the doctor hopes to rewrite the denouement.

Skin in the Game

What you don’t know about melanoma can kill you.

Sunblock. Initial mutations in melanoma occur as a result of intense sun exposure in childhood. A secondary mutation, caused by a sunburn as an adult, can promote melanoma to form. Wear sunscreen. Seriously.

Desk jockeys. Melanoma disproportionately affects professionals who work indoors—doctors, lawyers, dentists, executives, journalists, graphic designers, typical cube dwellers—because their skin does not have enough protective melanin (which comes from getting tan gradually instead of getting burnt to a crisp on a rooftop patio in LoDo on a Saturday afternoon).

Got a funny feeling. Melanoma can cause an immune reaction in a mole—even one you’ve had forever—that causes it to itch. Don’t ignore the sensation; go to the doctor.
Seeing spots? Melanoma usually presents as a mole. Monitoring moles for melanoma means knowing the ABCs of the disease. Moles should not be asymmetric; they should not have irregular borders; and they should not change color from a uniform brown.

Playing hide and seek. Melanoma occurs most often in women on the extremities and in men on the trunk. The disease is common on the head and neck in both sexes.

Scary different. Melanoma is not like other skin cancers. Mutated melanocytes grow downward underneath the skin and get into the bloodstream, where the microscopic disease can easily spread to the rest of the body.

Digging down deep. Melanoma that has burrowed into the skin by more than one millimeter has a greater propensity to spread. Doctors will remove the melanoma, measure it, and determine if a biopsy of the closest (aka sentinel) lymph node is necessary.

Inside Medicine

All In A Day’s Work

Dr. Julie Zimbelman, a pediatric oncologist and hematologist at Rocky Mountain Hospital for Children (RMHC), takes care of about 450 kids with cancer or blood disorders at any given time. Coming from a family of health-care professionals, it’s what she was born to do. Still, it’s not an easy job. “My husband once told me I’m the best and worst person for this career,” Zimbelman says. “He thought my heart would be so into it I wouldn’t be able to separate myself. But I’ve learned to be able to look at it from the perspective that it’s my job to care for these kids.” And that’s what she does from early morning until late at night. Here, a look at her typical day.

3:30 a.m. The phone rings. It’s one of the many calls I get overnight; a patient of mine, who is on chemotherapy, has a fever. Admission to RMHC is warranted. I notify the charge nurse on the inpatient unit and speak with the hospitalist.

4 a.m. My youngest child has a bad dream and needs consoling. As tired as I am, I love these stolen moments with my son when everyone else is sleeping. Because I know what I know, I never take for granted the gift of holding my children.

5 a.m. My alarm goes off.

6:30 a.m. I leave for work.

7 a.m. I arrive at a Cancer Committee meeting at RMHC.

8:15 a.m. I arrive at my office. I update the nurses on any call issues from the night before; sort through my inbox; and deliver reports requiring intervention or a phone call to our nurses.

8:30 a.m. I head to the infusion center to see an eight-year-old boy with leukemia. He’s here for IV chemo, which he receives monthly. I verify with his father that the youngster has taken his oral chemo and other meds as prescribed. I look at his labs, examine him, and talk with the nurses. I approve his chemotherapy. I love to see this boy and his father; their love is palpable.

9 a.m. I see a 14-year-old girl with leukemia who is here for chemo, including a spinal tap with instillation of chemotherapy. This teenager is nearing completion of two-plus years of chemo and is counting down the number of spinal treatments she has left. The anesthesiologist greets her and her mother as old friends; she is placed under anesthesia, and I perform the lumbar puncture. The yellow liquid is toxic, but also life-giving.

10:10 a.m. I run back to my office to see a two-month-old boy with Rh isoimmunization (a blood condition that develops in utero), whom I first met as a two-day-old. The baby required numerous intrauterine transfusions. He is beautiful but pale—his red cell production is decreased because of the transfusions. I admit him as an outpatient to our infusion center for a blood transfusion and reassure his parents his need for transfusion will not be life-long.

10:30 a.m. I see a teenage boy from out of state with lupus who has hematologic manifestations, including low blood cell counts and bleeding and clotting complications. His lupus is now under control on medication, he’s doing really well, and he’s graduating from high school and moving away. This is my last visit with him, and after years of being his hematologist I’m a little sad. He and his mom and I share hugs and tears as we say good-bye.

11 a.m. A patient is late for her appointment. I’m able to go through my inbox. I see I have an online class on safety in the workplace to listen to—but that
will have to wait. I sign medication refill fax forms, write orders for chemo, co-sign my partners’ orders, and fill out Family Medical Leave Act paperwork for a mother whose son has a sarcoma. I sign a Make-A-Wish form for a teenage patient.

11:30 a.m. I see a longtime patient of mine who is 10 years off therapy for Stage 4 neuroblastoma. It’s a reunion of sorts when I see these kids and their families. We have shared sacred moments.

Noon I see my three partners at a tumor conference. They are remarkable doctors and wonderful people. Throughout the course of the day we engage in discussions about patient care and ask the advice of one another.

1 p.m. I go to radiology to review scans on a patient of mine with a history of rhabdomyosarcoma (a soft tissue cancer that begins in immature muscle cells), first diagnosed as a baby. While he is many years out and this is his last set of planned imaging studies, I’m anxious. He relapsed years ago, and I pray his studies are clean. They are, but as I enter the room, his mom looks at me with worry. I’m relieved I can tell her everything looks good.

2 p.m. I see a new three-year-old patient with low platelets, likely a result of a viral infection. Her numbers are not low enough to require intervention, though she will need to be followed. Her parents are relieved she does not have cancer.

3:10 p.m. I get a call from the hematopathologist; a young patient of mine with newly diagnosed leukemia is in remission.

3:15 p.m. I see an 11-year-old girl with a hereditary hemolytic anemia. I have been her hematologist since she was a baby, and it is fun to see her. She’s so spunky. I love that she can tell me about the pathophysiology, genetics, and management of her diagnosis.

4 p.m. I receive a call from the radiologist regarding a patient with Ewing sarcoma who underwent surveillance imaging. Her studies show relapse disease. It’s soul-crushing. I go to review the scans directly; I am sad and angry at cancer. I go back to my office and consider further therapies—I email colleagues around the country and look into various research alternatives. I want to get all of the information I can to present to the family. I take a deep breath and pray for guidance as I plan to share devastating news.

6:30 p.m. I leave the office with plans to finish my patients’ charts once we’ve had dinner and my kids are asleep.