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Precision medicine unlocks the answers inside you

Written by Matt Windsor and Charles Buchanan for UAB Magazine. Illustrations by Christopher Davis.

You’ve heard it from kindergarten teachers, self-help books, and significant others: You’re one of a kind. Unique from head to toe.

Now you’ll hear that from your physician. Because the era of precision medicine is here.
What is precision medicine? Consider your next-door neighbor. You may share a fence, a ZIP code, and a love of cookouts. Perhaps even a diagnosis of high blood pressure. But your treatments might not be the same, all because of one gene mutation that makes Treatment A more effective for you, while Treatment B works better for her. The goal of precision medicine is to discover your unique attributes and mold health care to match your needs. It’s a revolutionary approach: The patient becomes the source of solutions for predicting, preventing, and treating disease.

UAB has leaped into a leading role in precision medicine, making the dream of truly individualized care a reality for Alabamians today. Follow along as we share some early successes and look ahead to exciting breakthroughs that could help you live your one-of-a-kind life to the fullest.

 


 

Finding the origin of the solution

Matt Might, Ph.D.

“Matt Might” sounds like a superhero’s name. He certainly is one to his son Bertrand, born with a mysterious disease that not only caused pain and seizures, but wouldn’t even allow him to cry. He could wail, but no tears would come.
After years of traveling to clinics to seek a diagnosis, Matt Might, his wife Cristina, and Bertrand all underwent exome sequencing—DNA sequencing that focuses on the expressed genes in a genome. There they found their answer: Bertrand had mutations that had destroyed the function of the NGLY1 gene. Bertrand “was the first human ever diagnosed with missing this gene and having it linked to a disease,” Might says. “Then the question became, can we treat it?”

Might, a Ph.D. and computer science expert, applied his knowledge of viral marketing, search engine optimization, and social media to seek others like Bertrand. Online, Might found families struggling with NGLY1 deficiency and scientists volunteering to search for potential therapies. Together, they learned that without a functioning NGLY1 gene, Bertrand and the others are deficient in a glucose derivative called N-acetylglucosamine—which can be purchased on Amazon. After testing it on himself, Might began giving it to Bertrand. Three days later, Bertrand was crying—with actual tears rolling down his face. The mighty Mights had won their first battle. And Matt Might was ready to harness the power of precision medicine to help other families searching for answers.

Last year, Might became the inaugural director of UAB’s Hugh Kaul Precision Medicine Institute, bringing stellar credentials to Birmingham. President Barack Obama appointed him to the White House Precision Medicine Initiative in 2015. He also held faculty positions at the University of Utah, where he specialized in computer science and pharmaceutical chemistry, and Harvard Medical School, where he was a visiting professor of biomedical informatics. His goal is to use computational technologies such as genomic sequencing to discover the best way to treat a specific person’s disease. “I tell people I’m developing the algorithm for precision medicine,” he says. “The input is the patient.”

Might says he is “terrifically excited” to be at UAB, with its “constellation of resources” and partnerships that place Alabama ahead of the curve in bringing precision medicine to patients. Supported by the Hugh Kaul Foundation’s $7-million investment in the institute, Might is recruiting research leaders “to get the right drug to the right patient at the right time.”

Precision medicine will reshape the search for those drugs, as in Bertrand’s case. “A big component is repurposing—testing the library of several thousand Food and Drug Administration-approved drugs to find out if they have other effects that are clinically beneficial, for diseases they were never originally intended to treat but actually do,” Might explains. He also foresees a more customized approach to the discovery and development of new drugs—one driven by patients armed with genetic data.

“We’ve established a blueprint for using precision medicine to go from disease discovery to therapeutic identification within one year,” Might says. “At UAB, we’re scaling it up in a big way.” This means that someday soon, he adds, no patient or family will hear a clinician say, “There is nothing we can do.”

 


 

Sequence of breakthroughs

Cancer is a disease with a thousand faces. Take breast cancer, for example. It’s not just breast cancer anymore. Instead, it might be breast cancer driven by a BRCA2 gene mutation, or breast cancer with elevated levels of the protein HER2/neu. And on and on.

The goal of precision oncology, says Eddy Yang, M.D., Ph.D., is to pinpoint these specific defects—to recognize the face within each patient. Yang is the ROAR Southeast Cancer Foundation Endowed Chair in Radiation Oncology, vice chairman for translational science in the Department of Radiation Oncology, associate program leader of experimental therapeutics in the Comprehensive Cancer Center, and deputy director and associate director for precision oncology in the Hugh Kaul Precision Medicine Institute.

Precision oncology is nothing new at UAB’s trailblazing Comprehensive Cancer Center. Beginning in 2013, Yang has met each month with fellow clinicians and scientists to review records of patients whose advanced cancer isn’t responding to traditional therapies. Then the group, the Molecular Tumor Board (MTB), decides whether to send cases out for genetic sequencing to help identify a new course of action.
One patient, Yang recalls, had salivary gland cancer, and had run out of treatment options. But DNA sequencing ordered by the MTB identified an intriguing clue: The patient’s tumor had a mutation commonly seen in melanoma, a form of skin cancer. That suggested a new melanoma-based treatment option, which brought the patient remission for more than a year.

The MTB serves as a national model for incorporating precision oncology into standard practice—and has yielded some remarkable results. Still, “sequencing isn’t a magical cure,” Yang notes. “We’re not going to find drugs for every person whose tumor we sequence, but we may be able to offer better treatment options for some patients.” Drug development is happening at such a rapid pace that a few extra months can make a big difference. “Sometimes we’re trying to buy patients enough time to get to the next new treatment,” Yang says.

Through a partnership with Michigan-based Strata Oncology, UAB cancer patients with tumors that can’t be removed surgically or that have spread to another part of the body can receive no-cost tumor sequencing. The trial is also available to all glioblastoma and pancreatic cancer patients, although any tumor type is eligible.

“We now sequence 50 to 60 patients per month” through the Strata Trial, and around 70 percent have a “tumor-driver” mutation, Yang says. Of those, around 20 percent will receive an off-label drug or be enrolled in a clinical trial of a new drug. For a sizable number, sequencing lets doctors “know what drugs not to give,” he adds. UAB patients also have access to more than a dozen new targeted therapies through another study, the TAPUR trial run by the American Society of Clinical Oncology.

UAB researchers say it’s only a matter of time before all cancers are treated based on their genomic abnormalities. “That’s the beauty of trials like Strata,” Yang explains. “For lung and colon cancer, ordering sequencing is almost reflexive for doctors. Now we can be reflexive for other types of cancer as well. Precision medicine is our standard of care.”



 

How cancer advances precision medicine

For decades, Michael Birrer, M.D., Ph.D. (at left in photo), has unraveled the molecular beginnings of gynecologic cancers. At the National Cancer Institute, and at Massachusetts General Hospital, Birrer’s lab has worked on prevention, early detection, and treatments for ovarian, cervical, and endometrial cancers based on their genomic characteristics. Now, as the UAB Comprehensive Cancer Center’s new director and the Evalina B. Spencer Chair in Oncology, Birrer is poised to play a key role in spreading the benefits of precision oncology to patients across the South.

How has this approach changed cancer treatment already?
Birrer: “Precision oncology is the poster child for precision medicine. For essentially every tumor in which scientists have validated a bonafide target and clinicians have used a small-molecule inhibitor, patient treatment has seen a huge impact. This is an exciting time in oncology—the most exciting time in my career. Things are moving very fast.

“Because these treatments are so narrowly targeted, their toxicities are narrow, which is good for patients. You may be able to change what ostensibly is a fatal disease into a chronic disease.”

How can UAB and Birmingham become precison oncology leaders?
Birrer: “We need clinical trials exploiting our molecular discoveries for every tumor type at every stage of the disease. We have about 500 patients per year on trial today; I want to increase that to 1,500 so that we become the clinical trials center for the South. That requires investment in everything from staff to space, but it benefits patients, and it could also attract major pharmaceutical and biotech companies to Birmingham.”

 


 

Alabama leads the way

Bruce Korf, M.D., Ph.D.

The body’s genetic blueprint, containing some 6 billion characters, is remarkably similar from person to person. But major sequencing studies have shown the potential for millions of differences between individuals, sometimes as simple as the genomic equivalent of a comma where a period should be.

Most changes seem relatively benign. But which ones should raise red flags for physicians? Would entire groups of people benefit from genetic testing? When are those tests most useful?

The Alabama Genomic Health Initiative (AGHI)—among the first projects of its kind nationwide—aims to find answers as it brings cutting-edge genomic medicine to every corner of the state. It is a collaboration between the School of Medicine and Huntsville-based HudsonAlpha Institute for Biotechnology, initially funded by $2 million from the Alabama Legislature to UAB. AGHI is recruiting a diverse group of participants from every county—2,000 in the first year, with a goal of 10,000 over five years. A simple blood draw from each participant will be tested for mutations in genes where a finding can lead to potentially life-saving intervention. The collected samples also will be stored in a biobank, helping researchers to uncover new links between gene variants and disease.

This landmark project “will result in immediate health benefits to some participants,” says Bruce Korf, M.D., Ph.D., UAB chief genomics officer and the Wayne H. and Sara Crews Finley Chair in Medical Genetics. “Long term, it will help address chronic disease and rising health care costs in the state, and position Alabama at the forefront of 21st-century medicine.”

The goal is “to develop a representative cross sample of residents, broadly characteristic of ethnic, racial, and socioeconomic groups throughout the state,” adds Matt Might, who is AGHI co-director along with HudsonAlpha’s Greg Barsh, M.D., Ph.D. The data will help diversify the standard reference genome used by researchers, which is largely composed of genomes from European backgrounds, Might explains. “That is essential to bring the benefits of genetic testing to all Alabamians.”

Each participant’s blood sample will undergo a genotyping array test, which assesses 650,000 identified genomic biomarkers for variants in “actionable genes” identified by the American College of Medical Genetics and Genomics as linked to an established intervention. (Currently the list includes 59 genes.) “The best-known genes on the list are BRCA1 and BRCA2, associated with a risk of breast and ovarian cancers,” Korf says. Others include genes associated with risk for heart disease, hypercholesterolemia, and a life-threatening adverse reaction to certain anesthetics, among other conditions.

Participants testing positive for a variant in an actionable gene receive genetic counseling, and they can share results with their primary medical provider to discuss prevention or treatment strategies. Based on previous studies, the number of participants likely to get positive reports will be small—maybe 1 to 3 percent, Korf says. But “the results will be life-changing and possibly lifesaving,” he notes. “It allows family members to take appropriate action as well.”

For any person showing signs of a genetic issue of undetermined origin, experts will analyze all 22,000 genes and 6 billion DNA base pairs, a process called whole genome sequencing, at HudsonAlpha to try to uncover a gene variant offering a clue to the disease. Those participants will receive results and links to appropriate care, which could include UAB’s Undiagnosed Diseases Program (UDP). Led by Korf, the UDP has assisted more than 160 patients since its 2013 launch. More than half who have completed evaluation have received a diagnosis, the result of cutting-edge genetic technology combined with traditional strategies such as a comprehensive review of medical history and extensive interviews with patients and families. “It’s great when you can tell somebody after all this time, ‘This is what you have,’” Korf says.

In addition to AGHI, UAB is part of All of Us, a research program led by the National Institutes of Health (NIH) to gather genetic data from more than 1 million people in the United States. “It provides a chance for individuals in our region to participate in an exciting initiative intended to provide new insights into prevention, diagnosis, and management of diseases across the nation.,” Korf says.

 


 

Intelligent medicine

Precision medicine is powered by information—minute details about patient genomes, medical and family history, lifestyle, environment, and so forth. Then there are the reams of medical research published each year—in 2014, there were 3 million new studies published on cancer alone. In that deep ocean of data, how will your doctors find the droplet of knowledge that helps them determine the most effective treatment for you?

They’ll identify it through informatics, or “the art and science of organizing knowledge of human health and disease, and making it useful for problem solving,” explains James Cimino, M.D., director of UAB’s Informatics Institute and the School of Medicine’s Endowed Professor in Informatics. In practice, that involves having a librarian’s fixation on order and classification, and a physician’s eye for picking out key details and observations.

Cimino has both. As a pioneering digital physician, he helped build DXplain, a landmark diagnostic support program used in medical schools, and invented infobuttons, smart links embedded in a medical record that offer vital context—contraindications or dosing guidelines when a doctor orders a new drug, for example. Cimino came to UAB in 2015 from the NIH, where his Laboratory for Informatics Development designed a system to let researchers query four decades of research data to find new insights and developed a method to link patients’ genomic data to their electronic health records.

Cimino has assembled a formidable team of UAB researchers to take on a similar challenge. “You can’t just collect data and expect it to speak for itself,” says Jake Chen, Ph.D., who joined the Informatics Institute in 2016 as associate director and chief bioinformatics officer. “It is challenging to sift through unless you have informatics practices—computers, prior knowledge databases, experts who know what they are looking for.” Ultimately, informatics will give researchers and clinicians more power to model complex diseases and observe outcomes of experimental therapies prior to human clinical trials, he says.

One top project for the Informatics Institute is AGHI. Analyzing genetic information from 10,000 Alabamians generates “a lot of data to manage,” Cimino says. The information is stored in a special repository so researchers with appropriate access can use it to identify participants for future studies. “For example, they can search for people with a certain condition who fail to respond to the usual therapy, and then obtain their genetic data to look for clues about the reason for failure,” says Cimino, who also co-directs UAB’s Center for Clinical and Translational Science. “Since many subjects will be UAB patients, researchers can access clinical data as part of their electronic health records.”

The transformative power of informatics lies in “intelligent medicine”—connecting the deep knowledge of biological systems from basic science researchers with the clinicians who can put it into practice, Chen says. “Informatics is really a discovery hub.”

Editorial contributors: Ryan Broussard, Kendra Carter, Cary Estes, Jane Longshore, Bob Shepard, Sarah C.P. Williams

Brain tumor therapy is going to the dogs

Renee Chambers, DVM, M.D.

People share many things with the dogs in their lives. Unfortunately, that can include a tendency to develop brain tumors. Dogs and humans are among the few species that spontaneously develop naturally occurring brain tumors. Those tumors have a lot in common, too, which has led scientists at the University of Alabama at Birmingham to wonder whether studying tumors in dogs will help treat humans, and whether studying tumors in humans will help treat man’s best friend.

“Brain tumors in dogs and humans are remarkably similar,” said Renee Chambers, DVM, M.D., professor in the Department of Neurosurgery at UAB School of Medicine. “They share similar rates of incidence and mortality, and they share similar symptoms such as seizures, which is often the first symptom observed in both humans and dogs. Treatment is very much the same too, with surgery, radiation and chemotherapy the standard of care.”

Chambers, who is a veterinarian as well as a UAB neurosurgeon, brings a unique perspective on the link between human and canine tumors.

“There are many shared factors between people and their pet dogs,” she said. “Dogs live in our houses, sharing the same environment and the same sleep patterns, for example. Some lucky dogs even share their owner’s diet. It is not unreasonable to assume that the dog will be a highly useful model of human brain tumors.”

And vice versa. Chambers says that, because of the similarities, new therapies being developed for humans might work on dogs. To that end, UAB is partnering with veterinary schools to conduct the first immunotherapy study for brain tumors in pet dogs using an oncolytic herpes simplex virus known as M032.

M032 was developed at UAB by neurosurgeon James Markert, M.D., who has been studying viral therapies for brain tumors for more than 25 years. M032 is a second-generation virus, following on the heels of a previously genetically engineered virus known as G207.

“Dogs live in our houses, sharing the same environment and the same sleep patterns, for example. Some lucky dogs even share their owner’s diet. It is not unreasonable to assume that the dog will be a highly useful model of human brain tumors.”

“Both G207 and M032 have been engineered to minimize the production of any toxic effects for the patient receiving the therapy,” said Markert, chair of the UAB Department of Neurosurgery. “Both are now in human studies, an M032 study in adults at UAB, along with a companion pediatric study of G207 underway at Children’s of Alabama. These studies mark the first time one institution has conducted trials of genetically engineered herpes virus in both adult and pediatric — and now canine — populations.”

Research funding from the National Institutes of Health for studies of G207 and M032 have helped to push the Department of Neurosurgery in to the top ten in NIH research funding nationally, according to 2017 figures from the Blue Ridge Institute for Medical Research.

Chambers is working with a network of regional colleges of Veterinary Medicine, including Auburn University, University of Georgia and Mississippi State University, to use M032 to treat their canine patients with naturally occurring brain tumors. Veterinarians at those institutions will use M032 under guidelines established at UAB, which serves as the coordinating center for the study.

“We anticipate that M032 will be as safe and effective in dogs as it is proving to be in humans,” Chambers said. “It opens up an exciting new research pathway, while providing the potential of a therapy that could benefit both humans and canines with brain tumors.

The five-year, $2.6 million project is funded by the Comparative Oncology Program of the National Cancer Institute. The goal is to treat about 14 dogs per year at the participating veterinary schools.

“The hope is that this research will benefit both dogs and people,” Chambers said. “Given the relatively short lifespan of the dog compared to a human, the timetable for results is accelerated. We talk of ‘translational medicine,’ moving research from the laboratory bench to the hospital bedside. This project is a revolution in the approach, also translating research findings from human to animal and back to human, to the benefit of both.”

The M032 virus has been designed to infect tumor cells while leaving healthy cells alone. It then replicates in the tumor cell, which kills the cell and causes it to act as a factory to produce new viruses. As the tumor cell dies, progeny viruses are released from the cell. These viruses infect other tumor cells in the vicinity and continue the process of tumor killing. But M032 also has a secret weapon — the virus was engineered to carry the human gene for interleukin-12, a powerful protein that stimulates and activates killer T lymphocytes that are part of the patient’s own immune system.

“This protein is expressed in the infected tumor cell as the virus is replicating,” said G. Yancey Gillespie, Ph.D., professor of neurosurgery and co-investigator. “Interestingly, dog T cells are also activated by human interleukin-12. It is our hypothesis that stimulating the immune system within the tumor bed itself, rather than systemically, will have a long-lasting anti-tumor effect, even after the virus has gone.”

“The body’s immune system is designed to patrol for foreign cells in the body, including mutated cancer cells,” Markert said. “The immune system’s cells have an off-switch, known as a checkpoint. The checkpoint keeps T-cells in ‘off-mode’, keeping them from attacking healthy cells. It is supposed to turn the T-cells on in the presence of a foreign cell or threat, prompting them to attack.”

Markert says tumor cells are very good at fooling the checkpoint so T-cells remains in the off-mode. Drugs known as checkpoint inhibitors turn T-cells on, stimulating them to attack the tumor.

According to Chambers, the first step of the new project will be to determine an optimal and safe dose of the virus for canine patients. “We will then combine this therapy with a checkpoint inhibitor, which is expected to keep the immune system ‘turned-on’ to capture and kill even more tumor cells,” she said.

Study investigators David Crossman, Ph.D., and Mike Crowley, Ph.D., will also conduct genomic sequencing of the tumors to determine how the dog’s genome predicts response or toxicities. Any mutations that are present in both the dog tumors and the human tumors will be studied further to discern their significance in the development of the tumor and their value as potential targets for new therapies.

“This work is important not only to canine brain tumor therapies but also to devising safer and more effective therapies for humans,” Chambers said. “It will critically inform the medical community on whether this combination approach, using an oncolytic virus followed by a checkpoint inhibitor, will be the next step in the successful treatment of brain tumors in both people and pets.”

Dine for a Cure at MELT on April 25

On Wednesday, April 25, MELT, at 4105 Fourth Ave. South, will host Dine for a Cure, a fundraising effort in which local restaurants partner with the Young Supporters Board of the University of Alabama at Birmingham Comprehensive Cancer Center to raise money for cancer research at UAB.

MELT will donate 10 percent of all proceeds from 6 p.m. to close to the Cancer Center’s Brown Family Fund, named to honor a Young Supporters Board member and her family who have been affected by the disease. The fund provides educational materials, supplies and equipment to support patients and their families visiting the Patient and Family Resource Center at the UAB Cancer Center.

The Young Supporters Board was established in 2006 to introduce the next generation of Alabamians to the importance of cancer research and awareness. The board comprises up-and-coming professionals between the ages of 22 and 40, all of whom have been touched by cancer in some way.

Cancer Center and Rotary Club of Birmingham work to end cervical cancer in Sri Lanka

From left: Isabel Scarinci, Ph.D., Edward Partridge, M.D., and Susan Jackson, executive director of the Birmingham Rotary Club.

The UAB Comprehensive Cancer Center and the Rotary Club of Birmingham are joining forces with the Rotary Club of Colombo and the Sri Lankan Ministry of Health to eliminate cervical cancer as a public health problem in Sri Lanka. If successful, Sri Lanka will be the first country to achieve such a goal.

Cervical cancer is the second most common cancer in women worldwide, and second among women in Sri Lanka as well. The disease is preventable through age-appropriate HPVvaccination and screening, yet unnecessary deaths continue to occur. Prevention tools and strategies are in place to eliminate the disease; however, adopting the practices still poses a major health problem.

“UAB, a leader in health care and education, has the ability to expand on its existing international partnerships to address relevant global health issues such as cervical cancer prevention and control,” said Edward Partridge, M.D., a former director of the UAB Comprehensive Cancer Center who is currently representing the Rotary Club of Birmingham in this effort. “This is a true public-private partnership where UAB, with its historical knowledge, can provide the scientific expertise for this initiative.”

The key to cervical cancer prevention is having a catalyst to mobilize organizations and communities around a common goal. “This movement is no longer in the hands of the medical community, as cervical cancer screening and vaccination discoveries are already in existence,” said Isabel Scarinci, Ph.D., professor in the UAB Division of Preventive Medicine and associate director for Globalization and Cancer at the UAB Comprehensive Cancer Center. “There are many socio-economic reasons and cultural reasons that stand in the way of adherence, but we can institute evidence-based practices that can legitimately move the needle.”

“Together, significant progress has been made toward a comprehensive cervical cancer prevention and control plan in Sri Lanka, and implementation steps are underway to be the first country to eliminate cervical cancer as a public health problem.”

As a polio survivor, Scarinci has witnessed firsthand the ability of Rotary International to serve as a champion to motivate communities around the polio vaccine worldwide. “If we look to PolioPlus as an example, it was not just the vaccine that eliminated polio, it was social mobilization,” Scarinci said. “The same thing can be done with cervical cancer and other HPV-related cancers, if the scientific, public and private sectors can combine efforts and expertise.”

The Rotary clubs of Birmingham and Colombo have a longstanding partnership and together have worked to establish the first regional cancer prevention and early detection center in Sri Lanka. Given that these clubs are already tackling cancer prevention, this presents an opportunity to potentially integrate low-cost cervical cancer prevention, screening and treatment activities into existing health care programs from an evidence-based perspective.

“Successful progress reports from the Rotary clubs’ breast cancer early detection project — along with some strong indicators from the population itself — partially inspired Ed Partridge’s suggestion to tackle cervical cancer in Sri Lanka,” said Susan Jackson, executive director of the Rotary Club of Birmingham “Ed’s passion in leading the Rotary Cervical Cancer Project–Sri Lanka is more than matched by Isabel’s, whose knowledge, experience and energy are critical to the training and the education that are central to the mission of the project.”

Recently, representatives from the UAB Comprehensive Cancer Center Globalization and Cancer Initiative along with Rotary Club of Birmingham members met in Sri Lanka with representatives from the Rotary Club of Colombo, the Sri Lankan Ministry of Health, the World Health Organization and Rotary International to unveil the plan.

It was determined that the team from the United States, utilizing the expertise of Rotary Club of Birmingham and UAB, could assist with social mobilization, education and awareness strategies, and the development and implementation of specific culturally relevant strategies to reach women who are not responsive to broader efforts.

“Together, significant progress has been made toward a comprehensive cervical cancer prevention and control plan in Sri Lanka, and implementation steps are underway to be the first country to eliminate cervical cancer as a public health problem,” Scarinci said. “And this is not only exciting but promising for other countries to emulate.”

Spindle cell sarcoma: rare but not to be ignored

JC Cunningham, left, and Michael Flanagan, M.D., on the trail.

Backpacking is hard enough without a softball-sized tumor in your leg. Not that it stopped JC Cunningham from tackling a section of the Appalachian Trail near Wesser, North Carolina, last Memorial Day. His hiking partner — a physician — had other thoughts.

“My left leg had swelled up a good bit,” Cunningham recalled. “My friend said my left leg looked like Earl Campbell’s, while the right one looked like a stick figure.”

About three months earlier, in March of 2017, Dothan native Cunningham and his teen-age son were removing a hard top from a Jeep. The son started to lose his grip and Cunningham took the weight on his left leg.

“We were about to drop it, and it’s too expensive for that, so I braced it on my leg,” Cunningham said. “I developed a large bruise that just kept getting worse. Of course, as many people tend to do, I ignored it.”

Until his hiking buddy, Michael Flanagan, M.D., got a look at it. Flanagan sent Cunningham straight to an orthopedic surgeon in Dothan, Patrick Guin, M.D. Guin suspected a tumor called a spindle cell sarcoma. A big one.

Guin sent Cunningham to the man he calls “The Sarcoma King,” Herrick Siegel, M.D., an orthopedic surgeon at the University of Alabama at Birmingham who has specialized in treating soft-tissue and bone cancer for more than 15 years. A biopsy confirmed Guin’s suspicions of a sarcoma.

“Spindle cell sarcoma is a soft-tissue tumor that can start in the bone, often in the arms, legs or pelvis,” said Siegel, a professor in the Department of Orthopedic Surgery in the School of Medicine. “Soft-tissue sarcomas are rare in adults, accounting for less than 1 percent of all new cases of cancer.”

Sarcomas can be found almost anywhere in the body. According to the National Cancer Institute, about 50 percent of soft-tissue sarcoma cases occur in the arms and legs, 40 percent occur in the back and chest, and 10 percent occur in the head and neck. The American Cancer Society reports that about 13,000 new cases of soft-tissue sarcoma will be diagnosed in 2018.

The Cunningham family, son Tristin, Sherie, JC and daughter Dara.

Sarcomas can be quite serious. They can cause loss of a leg or arm, and have about a 30 percent mortality rate in advanced stages.

Guin had trained at UAB under Siegel, and knew UAB represented Cunningham’s best chance for a good outcome.

“As in most cancers, the key to successful treatment of spindle cell sarcoma is to begin therapy as soon as possible at a center that has experience in the condition,” Siegel said. “UAB is a sarcoma center and is the most experienced and comprehensive hospital in Alabama. The critical specialties, including orthopedic oncologists, musculoskeletal radiology, plastic surgery, radiation oncology and medical oncology, can all be found at UAB.”

Siegel says the cause of spindle cell sarcoma is unknown. There is a genetic predisposition; however, it is not commonly thought to be hereditary. Some rare, inherited genetic conditions are considered risk factors for soft-tissue sarcoma. They include familial adenomatous polyposis, retinoblastoma, neurofibromatosis type 1 and Li-Fraumeni syndrome.

Cunningham admits that he is a typical male and tried to fight through the pain and swelling.

“I’m a hairdresser and on my feet all day,” he said. “The pain was bad, but I thought I could tough it out. And I didn’t want to miss the backpacking trip.”

Although he delayed, he got to UAB and Siegel in time. CT imaging determined the tumor had not spread to other parts of Cunningham’s body, and he underwent five weeks of radiation to shrink the mass. Siegel then removed the soft-ball-size tumor from where it pressed against Cunningham’s femur in an operation Oct. 11.

“We had to remove a large part of the quadriceps femoris muscle to get all of the tumor,” Siegel said. “We monitor his progress every three months with magnetic resonance imaging and CT.”

Cunningham didn’t hesitate to begin recovery. He was walking in his hospital room the next day and was so excited by his progress that he sent videos of himself walking around his room to Siegel to prove it. He was raking leaves one week out from surgery and back at work in just over two weeks. Overall, he did six weeks of formal physical therapy.

UAB orthpedic surgeon Herrick Siegel, M.D., and Cunningham during a recent clinic visit.

“I’d never heard of a sarcoma before, and as my physician in Dothan described it to me, it became clear that I needed to go to the place that had the most experience in dealing with this type of cancer, and that meant UAB,” Cunningham said.

“His prognosis is excellent, with no sign of any remaining cancer,” Siegel said. “His positive outcome is centered on his good physical condition and the fact that we were able to remove the entire tumor before it had a chance to spread.”

Cunningham says he relied on his friends to help him navigate the often confusing and scary diagnosis of cancer.

“My friend Mike is a medical professional, and he took on the role of cancer navigator for me,” Cunningham said. “He helped sort through the confusion, the uncertainty and the questions. I really like the navigator concept.”

He says he’s back to doing most of the activities that he loves — hiking, hunting and playing with his kids. A Memorial Day backpacking trip is once again on the schedule.

“I’m thankful to have a leg and be alive,” Cunningham said. “I feel blessed even with all things I am dealing with. The end goal is to push back and return to a normal life, to where I was before.”

“I’m one of the lucky ones” — treating head and neck cancer

Walker’s husband, Tolly, was a constant source of support and care during her treatment.

May 2016 will be a time that Jan Walker will never forget.

Walker, a retired administrative assistant to the superintendent of Boaz City Schools, was getting ready for her regular doctor visit and noticed a lump on her neck. Her primary care physician examined it and determined it was a simple swollen lymph node. Two months later, she began to lose feeling on the right side of her throat and noticed the lump had increased in size.

After seeing other doctors for multiple opinions, she was sent to UAB Hospital, where she met with Department of Otolaryngology Assistant Professor Benjamin Greene, M.D., and found out something she had feared — it was cancer: oropharyngeal cancer, to be precise.

“I was really upset,” Walker said. “My mom lost her battle with breast cancer, and this just really scared me. The first initial shock of being diagnosed made me think I was going to die, but I’m one of the lucky ones.”

According to Greene, oropharyngeal cancer — the oropharynx includes the tonsils and base of tongue — is a fairly uncommon cancer in general. In non-smokers, in these particular areas, the cancer is usually caused by HPV. The Centers for Disease Control and Prevention reports that about 3,200 cases of oropharyngeal cancers were found in women last year and about 13,000 in men in the United States. Walker did not smoke or drink alcohol, which put her in a rare group when she received her diagnosis.

In general, the five-year survival rate of oropharyngeal cancer has been less than 50 percent,” Greene said. “Of course, this depends on stage at the time of diagnosis; however, we are finding that people who do not smoke or drink heavily do much better. In people who have cancer caused by HPV, the five-year survival rates can be 80-90 percent.”

The Walker family.

After receiving her diagnosis, Walker, a Glencoe, Alabama, resident, began her treatment plan in September 2016 and included 35 radiation treatments and five chemotherapy treatments. Doctors also had to put in a port and feeding tube because the radiation made Walker’s throat irritable. Her patient navigators helped set appointments with UAB speech therapists and nutritionists so she could learn how to cope with her new way of life during treatment.

“I had a feeding tube — which probably was the worst part about the treatment — but the doctors told me to be conscious about swallowing so I wouldn’t lose muscle control,” Walker said.

Greene says radiation and chemotherapy for the head and neck can be very hard on people.

“All treatments for this type of cancer can be potentially disfiguring and debilitating,” he said. “It can affect the way we eat, the way we speak and the way we look, as well as our general quality of life.”

After five months of treatment and multiple subsequent follow-up visits, Walker received the news that she was cancer-free in March 2018. She will still have to see her UAB physicians every three months, but she has a new outlook on life and on what could have been a completely disheartening experience.

“This has changed my outlook on life tremendously,” she said. “It has made me closer with God, and I realize now that we’re not promised tomorrow. It was tough on my husband, Tolly, and two sons; but we got through it. We’re much closer as a family.”

Greene says the most important thing people can do to prevent these types of cancers is to quit smoking. Even though HPV is causing more head and neck cancers, smoking is still the No. 1 cause of these diseases. Greene also says it is very important that people go to their doctors whenever they have a sore throat or hoarseness that won’t go away.

“Cancers of the throat can masquerade as many things, such as ear pain, sore throat, hoarse voice, difficulty swallowing, coughing up blood or loose teeth,” Greene said. “Anything that is concerning should prompt a visit to a dentist, primary care doctor or otolaryngologist. It is extremely important to note that any enlarged lymph node or enlarged gland in a person over 40 is not normal and should be examined immediately. In general, people who have their head and neck cancers diagnosed early do much better in the long run and often need less-aggressive treatment.”

The UAB Department of Otolaryngology stands among the nation’s leaders in its field. Physicians provide advanced care across the spectrum of head and neck disorders with surgeons practicing in six areas of specialty. For more information, visit www.uab.edu/medicine/otolaryngology.

UAB Cancer Center celebrates National Minority Health Month and National Minority Cancer Awareness Week, April 8-14

The University of Alabama at Birmingham Comprehensive Cancer Center has long been recognized as a leader in community outreach, most notably for its work in increasing education and awareness of cancer in minority and underserved populations.

Through its partnerships with local community leaders and other academic institutions, the Cancer Center is leading the way in reducing health care disparities among minorities.

“As we are the only NCI-designed comprehensive cancer center in a four-state region, it is critical that we address the disparities that exist in minority populations,” said Claudia Hardy, director of the Office of Community Outreach at the UAB Comprehensive Cancer Center. “These populations, specifically African-Americans and Hispanics, experience a higher cancer mortality rate, and at the UAB Cancer Center, we have the opportunity to serve a large minority geographic region.”

For more than 20 years, the UAB Comprehensive Cancer Center has created and perfected a unique model in which it uses community health advisers, or ‘natural helpers’ from the community to reach the medically underserved in those communities. These CHAs provide cancer awareness and screening messages and link resources to their communities. CHAs who are also trained to conduct multi-level participatory research help to develop, implement and evaluate education programs to reduce cancer health disparities.

“We’ve trained more than 1,200 CHAs to reach African-Americans and other medically underserved to include cancer screening, healthy lifestyles, environmental evaluations and community-based research interventions,” Hardy said. “Cancer is not an equal-opportunity disease. Many minorities must face this great burden without the resources they need.”

In observance of National Minority Health Month, the UAB Comprehensive Cancer Center is participating in community outreach events throughout Jefferson County. These events are free and open to the public. Events include:

  • Minority Cancer Awareness Week Expo: Monday, April 9, 8 a.m.-2 p.m., at the UAB Hospital North Pavilion, 2nd Floor
  • Meet the Cancer Center Director: Michael Birrer, M.D., Ph.D.: Tuesday, April 17, 5-6 p.m. at the JCCEO Festival Head Start Center, 6701 Crestwood Blvd.
  • 107 Days to Better Health Expo: Saturday, April 21, 10 a.m.-2 p.m. at the YMCA Youth Center, 2400 Seventh Ave. North

For questions regarding community events, contact Claudia Hardy at (205) 975-5454 or chardy@uab.edu.

Free oral, head and neck cancer screening set for April 13

Some 650,000 people are expected to be diagnosed with oral, head and neck cancer worldwide in 2018, and UAB physicians in the Department of Otolaryngology are hoping to get ahead of the game by offering a free screening event Friday, April 13.

Cancers of the head and neck are four times more common in men than in women, and early diagnosis can more than double a patient’s chances of survival. High risk factors include tobacco and alcohol use, exposure to HPV, and persistent neck mass or pain in the mouth or throat.

“Historically, cancers of the head and neck were found in adults over age 50; but we are now seeing these cancers affect a more diverse group of people,” said William Carroll, M.D., the John S. Odess Endowed Chair in Otolaryngology. “Everyone should be screened — especially if they partake in any of the major risk factors.”

The free screening will take place at The Kirklin Clinic on the fifth floor from 1-4 p.m. For more information, contact Morgan Samples at 205-975-1254 or mpsamples@uabmc.edu.

A new test for urothelial cancers is less invasive, more accurate

george netto 2018 streamA new test for urothelial cancers could detect mutations in DNA that have been identified for those cancers earlier than traditional tests. The earlier detection of urothelial cancer could lead to earlier treatment, and potentially better outcomes for patients.

The test, called UroSEEK, uses urine samples to seek out mutations in 11 genes that indicate the presence of DNA associated with bladder cancer or upper tract urothelial cancer (UTUC). The researchers say the test, when combined with cytology — the gold standard noninvasive test currently used for detection — significantly enhanced early detection for patients who are considered at risk for bladder cancer, and surveillance of patients who have already been treated for bladder cancer.

These findings were published online on March 20 in eLife.

“There were nearly 80,000 new cases of bladder cancer and more than 18,000 deaths in 2017,” said George Netto, M.D., one of the study leaders for UroSEEK and chair of the Department of Pathology at the University of Alabama at Birmingham. “This is about using the urine to detect the cancer. UroSEEK is a molecular, noninvasive method of detection.”

Netto helped lead the development of the new test in collaboration with his colleagues at Johns Hopkins Kimmel Cancer Center before joining UAB.

UroSEEK is aimed toward early detection of bladder cancer in at-risk patients — those who may have blood in their urine or people who smoke — and patients who have already gone through a procedure to treat bladder cancer and need to be monitored for any recurrence of the disease.

“In almost one-third of patients, bladder cancer detection is late,” said Netto, who joined UAB as chair of the Department of Pathology in 2016. “The cancer has already gotten into the surrounding muscle. Even in those detected at an earlier stage, the tumors frequently recur, thus, patients are committed to a lifelong surveillance that requires invasive cystoscopy procedure and biopsies and is costly.”

Bladder cancer is the fourth most common cancer in men, according to the American Cancer Society. Netto is a senior scientist in the Experimental Therapeutics program at the UAB Comprehensive Cancer Center.

R21 grant will explore new options for tobacco cessation

scarinci carroll

Isabel Scarinci, Ph.D., and William Carroll, M.D.

Despite smoking fewer cigarettes daily, African-American men suffer higher morbidity and mortality associated with tobacco-related disorders than Caucasians, according to University of Alabama at Birmingham researchers.

To remedy this problem, Isabel Scarinci, Ph.D., Young-Il Kim, Ph.D., from the UAB Division of Preventive Medicine and William Carroll, M.D., from the and Department of Otolaryngology, received an R21 grant to explore effective ways of implementing tobacco cessation in young African-American men living in rural counties in Alabama.

“Our preliminary data shows that 39.9 percent of African-American men in rural Alabama between 19 and 30 years of age smoke cigarettes, which is much higher than data provided by the Centers for Disease Prevention and Control among African-American men in the same age bracket in Alabama (15.5 percent),” Scarinci said.

Scarinci says that for many years the Deep South Network for Cancer Control has focused on breast and other cancer prevention and control among African-Americans in rural Alabama; but she was shocked when her colleague John S. Odess Endowed Chair William Carroll, M.D., noticed a spike in head and neck cancer cases in African-American men caused by tobacco use.

“The biggest thing is that we kept seeing this devastating disease from the same communities,” Carroll said. “That’s what motivated us to try to make a difference. We would like to interrupt this cycle in young people before the habits get too deeply engrained so that we might have a better chance of avoiding tobacco-related disease.”

Scarinci says that, if her team can prevent tobacco use before age 30 in this demographic, she is confident they can prevent more tobacco-related disease.To compile data about tobacco use in African-American men, Scarinci and Carroll — both members of the UAB Comprehensive Cancer Center, surveyed males age 19 to 30 in rural Alabama counties asking about their use of tobacco. What they found was that the percentage of young African-American men using tobacco was more than double the percentage of African-American men in the same age group using tobacco based on data provided by the Centers for Disease Prevention and Control for the state of Alabama (15.5 percent).

“We’re passionate about this research, because we are confident that by intervening early we can avoid the high number of head and neck cancers seen by Dr. Carroll and his colleagues,” Scarinci said.

With the grant, Scarinci and Carroll’s team will build local capacity in these rural areas by training community health workers to promote tobacco cessation with the support of UAB experts who can deliver and manage the pharmacological component through telehealth.

“We already know what works in tobacco cessation,” Carroll said. “It is the combination of cognitive-behavioral therapy and pharmacological management, but smokers in rural areas many times do not have access to these treatments. We’ve tried to set this up in a way to be scalable to other parts of the country. If we can find success with this group, it can give us a template for other areas.”