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Mayo Clinic Medical Science Blog – an eclectic collection of research- and research education-related stories: feature stories, mini news bites, learning opportunities, profiles and more from Mayo Clinic.

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Wed, Jul 11 10:00am · Mayo Clinic-led Study Finds Breast Cancer Survivors Aren't Getting Recommended Number of Mammograms Post-Surgery

Kathryn Ruddy, M.D., M.P.H.

Breast cancer survivors are not getting the recommended level of post-surgery screening, according to a study published in the May 2018 issue of the Journal of the National Comprehensive Cancer Network (JNCCN).  Contrary to screening recommendations, mammography rates decline over time as women get further out from their breast cancer diagnosis; African-American women in particular were less likely to receive the recommended amount of screening.

The study was led by Kathryn Ruddy, M.D., M.P.H., a Mayo Clinic medical oncologist in Rochester, Minnesota and co-chair of the Mayo Clinic Cancer Center Survivorship Cross-disciplinary Group. Dr. Ruddy is also a member of the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology Panel for Survivorship.

“The use of regular mammograms to detect a return of breast cancer before any symptoms appear is associated with better overall survival,” said Dr. Ruddy. “Therefore, clinicians need to make sure that their patients are fully aware of the role these annual mammograms play in screening for new breast cancers as well as for local recurrences. Creating and implementing survivorship care plans with clear follow-up instructions may help ensure that more survivors adhere to recommended screening schedules.”

The researchers followed 27,212 patients for a median of 2.9 years after breast cancer surgery (excluding those who had bilateral mastectomy, for whom mammograms are not needed), with 4,790 patients remaining in the study cohort for at least 65 months.

The retrospective analysis used the OptumLabs Data Warehouse, containing claims from privately insured patients and Medicare Advantage enrollees from across the United States. One year out from surgery, they found 13 percent of the survivors had not undergone any breast imaging. The number without a mammogram within the past year rose to 19 percent by five years after surgery.

Only 50 percent of the patients who were followed for at least five years had at least one mammogram each of those five years.

The study also found that African-American breast cancer survivors were less likely than their white counterparts to receive mammograms according to the recommended schedule. This may contribute to higher mortality rates for that population, given that recurrence of cancer in the breast is considered to be a major driver for poor prognosis in African-American women. While the reasons for this disparity aren’t clear, limited access to genetic testing could be a factor.

There are new tools currently in development to help support and encourage adherence to post-treatment screening guidelines, including mobile apps and web-based programs. Further research is needed to explore how variability in reimbursements for imaging tests may impact surveillance testing.

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This story is based on a May 24, 2018 news release provided by the National Comprehensive Cancer Network.

Mon, Jun 25 6:00am · Targeted DNA next-generation sequencing aids the molecular assessment of pancreatic neuroendocrine tumors

Non-specific image of pancreatic cancer.

Pancreas neuroendocrine tumors (pNETs) are a collection of rare neoplasms distinct from pancreas ductal adenocarcinoma. Although the molecular profile of pNETs is somewhat unclear, advances in molecular tumor genotyping is one area of research that is advancing the understanding of this disease.

In a 2017 article published in OncotargetFerga Gleeson, M.D., M.B., B.Ch., a specialist in gastroenterology and hepatology at Mayo Clinic’s campus in Minnesota, describes a targeted DNA next-generation sequencing (NGS) study conducted at Mayo Clinic.

“Alterations in MEN1 chromatin remodeling genes and mammalian target of rapamycin (mTOR) pathway genes are the most frequent molecular events identified in pNETs,” explains Dr. Gleeson, “But it’s unclear whether these biomarkers and other less frequently observed aberrations possess predictive value.”

The goal of the Mayo study was to assess tumor cytology genotype diversity via endoscopic ultrasound (EUS), and to survey for potential adverse prognostic biomarkers and the prevalence of mTOR pathway variants. “The premise of our research is that molecular tumor genotyping via EUS fine-needle aspiration has the potential to determine a specific tumor’s eligibility for targeted molecular therapy or perhaps immunotherapy, and to facilitate triage of patients into clinical trials based upon their respective tumor genotype,” explains Dr. Gleeson.

Methods

Researchers used a customized 15-gene gastroenteropancreatic neuroendocrine tumor targeted NGS panel evaluating EUS fine-needle aspiration cytology smears from primary pancreas pNETs (90) and pNET liver metastasis (32).

Results

The study yielded a number of interesting results that point to the utility of cytology-based tumor genotyping.

  • 21 percent of primary and 28 percent of metastatic liver pNETs harbored two or more variants per tumor.
  • The most prevalent primary tumor variants were in the MEN1 (42 percent), DAXX (11 percent), ATRX (10 percent) and TSC2 genes (8 percent).
  • Patients harboring aberrations in TSC2, KRAS or TP53 genes were more likely to experience disease progression and reduced overall survival, when compared with individuals who were wild-type.
  • Potential prognostic biomarkers in early disease were observed in 3.3 percent of the primary tumor cohort.
  • The mTOR pathway variants, including alterations in PTEN, TSC2 and PIK3CA, were identified in 10 percent of primary tumors and 12.5 percent of pNET liver metastases.

Conclusions

Ferga Gleeson, M.D., M.B., B. Ch.

This study provides evidence that cytology-based tumor genotyping can reveal a broad spectrum of genetic variants, including possible adverse prognostic biomarkers, reflective of an aggressive phenotype. It also demonstrated the prevalence of potential predictive biomarkers for mTOR pathway inhibitor sensitivity. “We are hopeful that such molecular profiling and patient stratification will become a vital aspect of future efforts to provide individualized and targeted therapy to enhance outcomes for appropriately selected patients,” explains Dr. Gleeson.

Additional research that Dr. Gleeson and colleagues are involved with demonstrates the utility and partnership of EUS with disease-specific and comprehensive cancer gene next-generation sequencing panels, both commercially developed and Mayo developed. When used together, these tools can enhance the evaluation of pancreas ductal adenocarcinoma, pancreas neuroendocrine tumors, gastrointestinal stromal tumors, lung cancer and melanoma.

“Our group’s strength is our collaborative partnership with colleagues in Mayo’s Center for Individualized Medicine and Department of Laboratory Medicine and Pathology to advance the field of DNA and RNA sequencing to further our molecular tumor genotyping capabilities. Our vision is that this will become part of standard clinical care in the field of precision medicine, to offer a customized approached to patient care based upon the molecular profile within a specific tumor or metastatic site.”

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This article was originally published in Cancer Physician Update, a quarterly publication for physicians that discusses trends and advances in hematology and oncology at Mayo Clinic.

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Mon, Jun 11 6:00am · Bioartificial liver: Potential to avoid transplant

Schematic of the extracorporeal circuit of the Spheroid Reservoir Bioartificial Liver

Mayo Clinic researchers are planning clinical trials of a bioartificial  liver that might eventually provide an alternative to transplantation for patients with liver failure. Known as the Mayo Spheroid Reservoir Bioartificial Liver (SRBAL), the novel device has been shown to reduce the severity of liver disease and improve survival in laboratory testing on pigs. (Bioartificial organs are comprised of both living tissue and synthetic materials).

“SRBAL has demonstrated ammonia clearance at vastly higher levels than the reports from earlier generations of bioartificial livers,” says Scott Nyberg, M.D., Ph.D., a liver transplant surgeon and biomedical engineer at Mayo Clinic in Rochester, Minnesota. “I foresee a day when we can use these devices as a bridge therapy to transplantation or even to support patients long term and avoid liver transplantation.”

SRBAL would be most appropriate for patients who:

  • Have acute liver failure and are awaiting transplant
  • Have had an overdose of medication, such as acetaminophen, but have a high probability of liver regeneration
  • Aren’t candidates for liver transplant due to another health concern such as cancer, or recent alcohol use

Patients who use SRBAL as a bridge to transplant might utilize the device for an average of one to five days, up to a maximum of two weeks.

Similar to hemodialysis in the treatment of kidney failure, Mayo Clinic’s bioartificial liver functions outside of the patient’s body. However, SRBAL is a “hybrid” extracorporeal device in that it contains hepatocytes of porcine or human origin as a biological source of liver function. The device can maintain functionality of primary hepatoctyes in the range of normal liver physiology — even at the high cell density required for human therapy.

“Our ability to successfully perform liver transplant surgery has led to our biggest problem in this field: the shortage of donor organs,” Dr. Nyberg says. “If we can devise new technologies to avoid liver transplant, we’ve achieved a major accomplishment.”

A quarter century of research

Scott Nyberg, M.D., Ph.D., uniquely trained as both a liver transplant surgeon and biomedical engineer, leads efforts to develop cell-based therapies for the treatment of patients with liver failure and metabolic liver disease.

Dr. Nyberg, who leads Mayo Clinic’s Artificial Liver and Liver Transplantation Laboratory, has devoted more than 25 years to developing the bioartificial liver. The idea came from a mentor during his medical training, who suggested that Dr. Nyberg combine his medical and engineering expertise. His recent research has received funding from the Regenerative Medicine Minnesota initiative.

“As a liver transplant surgeon, I see how serious liver failure is for patients of all ages,” he says. “Liver disease is a world problem. At Mayo Clinic, we’re leading the way internationally with the liver-support device. It’s quite an exciting time.”

The artificial liver and liver transplantation lab has extensive experience in isolating and cultivating primary hepatocytes for use in cellular therapies. The lab uses genetically engineered pigs with a homozygote deficiency in fumarylacetoacetate hydrolase (FAH) — the first large animal models of hereditary tyrosinemia type 1 (HT1) in hereditary metabolic liver disease. The phenotype of FAH-deficient also includes spontaneous cirrhosis, portal hypertension and possibly hepatocellular carcinoma. The porcine model could potentially allow for the large-scale production of high-quality human hepatocytes needed in order for bioartificial livers to be incorporated into clinical use.

About 38,000 people in the United States die each year from liver disease, according to the Centers for Disease Control and Prevention. “Acute liver failure claims the lives of over 30 percent of people who are diagnosed with it. Liver transplantation has been the go-to option for treatment, but it comes with many risks and isn’t always an option, due to compatibility and availability of donor livers,” Dr. Nyberg says. “A bioartificial liver device could allow physicians to treat and extend the lives of more patients, safely and cost-effectively, with fewer risks.

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This article was originally published in Cancer Physician Update, a quarterly publication for physicians that discusses trends and advances in hematology and oncology at Mayo Clinic.

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Thu, Mar 22 9:00am · Mayo researchers identify characteristics of colon polyps most likely to progress to cancer

Lisa Boardman, M.D.

Researchers at Mayo Clinic are closer to answering the question, why does one colon polyp transform to cancer while another seemingly identical polyp does not? A colon polyp is a small clump of cells that forms on the lining of the colon. While most colon polyps are harmless some can develop into colon cancer, which can be fatal if found too late.

“The molecular determinants that distinguish normal, benign polyps from those at risk for becoming cancer are unclear,” says Lisa Boardman, M.D. a gastroenterologist at Mayo Clinic. “In our paper, published in the journal Scientific Reports, we asked the question: why does one polyp transform to cancer while another, that is clinically and histologically identical, does not?”

To answer this question, Dr. Boardman and her colleagues used next-generation sequencing techniques to molecularly characterize and compare colorectal polyps from Mayo Clinic patients that were associated with cancer with those from patients with polys that were benign.

Next-generation sequencing is sophisticated DNA and RNA sequencing technology which allows researchers to study biological systems at a level never before possible.

Dr. Boardman and her colleagues found that polyps adjacent to cancerous tissue exhibited distinct genetic alterations from polyps that remained cancer free. “By integrating multiple sequencing platforms, we identified a panel of 124 genes that were differentially altered between polyps that were associated with cancer and polyps that did not progress to colorectal cancer,” she says. “These results serve as a foundational study showing that polyps with and without cancer exhibit distinct molecular signatures.”

Dr. Boardman says the ability to identify molecular features that predict whether a polyp will transform to cancer would be a major clinical step in individualizing the care of patients with polyps. She says current national guidelines for polyp surveillance are still based only upon polyp size, number, histology and degree of dysplasia. She adds that there are currently no blood or tissue-based molecular tests used to tailor surveillance intervals for patients with polyps.

Dr. Boardman says the ability to determine a polyp’s risk for progression to cancer could have significant benefits for patients and the health care system including reducing costs, reducing risks and improving the use of colonoscopy. “This study is also the first step in our efforts to establish a pre-cancer biobank at Mayo Clinic, which will support future studies on polyps in order to prolong health by preventing pre-malignancy in the colon.”

Nov 2, 2017 · Targeting a Molecular Abnormality

Microsatellite instability (MSI) might sound like something a NASA engineer would study. But it’s actually a molecular abnormality found in 15 percent of colorectal cancers, explains Mayo Clinic medical oncologist and gastroenterologist Frank A. Sinicrope, M.D., who is testing an immunotherapy drug that could help patients with this subtype of colorectal cancer.

Just recently, researchers discovered why colorectal cancer with MSI can evade the body’s immune system, grow and become lethal: checkpoint proteins present on MSI tumors allow the cancer to manipulate the body’s defenses.

Armed with this knowledge, Dr. Sinicrope and his team will conduct a national clinical trial to test whether a drug called an immune checkpoint inhibitor can prevent the cancer from dodging death. The trial will enroll patients with stage III colon cancer with MSI who have already had surgery to treat the cancer.

“There is a great deal of interest in the trial and a lot of optimism based upon remarkable results seen for immune checkpoint inhibitors in patients with metastatic colorectal cancers,” Dr. Sinicrope says.

Escaping Attack

Colorectal cancer with MSI is typically diagnosed at an earlier stage, and patients do better than those without the molecular abnormality. But the survival advantage is lost once the cancer spreads to other sites in the body.

MSI has a genetic basis. It results from the loss of function in one of the genes that repair errors in the DNA sequence when DNA is replicated. Tumors with MSI mutate rapidly, acquiring hundreds to thousands of mutations. This causes the immune system to kick into high gear. It recognizes the tumor and dispatches an army of T cells to attack. Yet the cancer has developed ways to escape this attack. Researchers observed this for many years and didn’t understand how it was possible.

Colorectal cancer with microsatellite instability (MSI) has specific features, including a tendency for tumors to be on the right side of the colon. MSI tumors mutate rapidly and grow to a large size.

Researchers now know that colorectal cancer with MSI can tap into checkpoints, an immune system pathway used to distinguish foreign cells from normal cells and signal whether or not to attack cells. Checkpoint proteins present on MSI tumors bind to receptors on T cells so those T cells can’t be activated in an attack. By exploiting the immune system’s checkpoints, MSI tumors can fly under the radar.

Immunotherapy prompts the immune system to refocus on fighting cancer. Immunotherapy drugs are new, but the idea of immunotherapy is not. Some of the foundational discoveries in checkpoints were made two decades ago in a series of experiments performed by Mayo Clinic researchers.

An immunotherapy drug called an immune checkpoint inhibitor is an antibody that blocks the cancer from evading attack and boosts immune response against the cancer. Such drugs have shown promise in clinical trials on metastatic colorectal cancer with MSI — when the cancer has spread to other sites in the body and is often fatal. The U.S. Food and Drug Administration approved in May 2017 the use of one immune checkpoint inhibitor for patients with this kind of cancer who have no other options for treatment.

Determined to change patient care, Dr. Sinicrope will test a checkpoint inhibitor called atezolizumab in a phase III trial, the only one to date focused on colon cancer before it metastasizes and turns lethal.

“We never had drugs before that could effectively modulate the immune system in order to achieve the outcomes that are being observed in certain tumor types,” Dr. Sinicrope says. In the trial, the checkpoint inhibitor will target micrometastases, tiny tumor cells left behind after surgery. These cells can’t be detected with conventional tests and are responsible for the return of the cancer.

The trial will enroll 700 patients at Mayo Clinic campuses in Rochester, Minnesota; Jacksonville, Florida; Scottsdale, Arizona; and at multiple other sites across the U.S. through the Alliance for Clinical Trials in Oncology. Some patients will receive the checkpoint inhibitor in addition to chemotherapy, and others will receive only chemotherapy. After treatment, which could last up to one year, doctors will monitor patients for recurrence and survival for three years.

Predicting treatment

In addition to seeking better therapies for patients, Dr. Sinicrope’s research focuses on cancer biomarkers.

Biomarkers are molecular substances found in body fluids or tissues that can alert doctors to disease. They are used increasingly in screening for the early detection of cancer. Biomarkers can also predict the likelihood of the recurrence or spread of cancer. And they can indicate whether treatment, like immunotherapy, may work in certain patients.

Frank A. Sinicrope, M.D.

MSI is considered a predictive biomarker for treatment with checkpoint inhibitors, Dr. Sinicrope says. Testing for MSI at the time of a colorectal cancer diagnosis is increasing around the U.S. and now is recommended for all newly diagnosed patients. MSI is seen in a range of other cancers as well, including endometrial cancer.

Discovering biomarkers like MSI and categorizing the immune composition of tumors can help transform patient care, Dr. Sinicrope explains. In the case of MSI tumors, the evolving perspective is to treat the molecular abnormality — not necessarily the tumor type, he says.

“This is the exciting area of precision oncology.”

This story originally appeared in the 2017 print edition of Forefront magazine.

Oct 26, 2017 · New Issue of Forefront Magazine

Forefront is the complimentary magazine of the Mayo Clinic Cancer Center. Published in print and online magazine editions annually and in email and online newsletter editions quarterly, Forefront highlights Mayo Clinic’s cutting-edge cancer research and the latest Cancer Center news.

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Oct 19, 2017 · Cycling Through Multiple Myeloma

Meet Andy Gordon, a health care litigator, dad, husband, cyclist, philanthropist and one in 14 million.

It was Labor Day 2009 when Andy received the same diagnosis his wife had heard 12 years earlier — a one in 14 million possibility. Andy’s wife Sue was diagnosed on April 11, 1997, with multiple myeloma, and she died on May 1. She never came out of the hospital. Their kids were 12 and 14 at the time.

Multiple myeloma is a blood cancer that forms in a type of white blood cell called a plasma cell. Plasma cells help you fight infections by making antibodies that recognize and attack germs. Multiple myeloma causes cancer cells to accumulate in the bone marrow, where they crowd out healthy blood cells.

“I was living in Washington, D.C., and riding my bike a fair amount when I started to have back pain,” recalls Andy. “I thought it was just middle-aged stuff.” The pain became unbearable while he was in Guantanamo Bay, Cuba, working for the U.S. Department of Homeland Security. In and out of planes and boats, he chalked it up to his activity, but he scheduled an appointment when he returned to the states just to make sure.

When the doctor couldn’t figure out the source of the pain, she sent Andy for a CAT scan. “I could tell just from the look on her face this is not going to be terrific news,” Andy says.

The doctor told Andy he needed to be hospitalized immediately. Andy had just turned 60 when an oncologist in the Washington, D.C., area confirmed he had multiple myeloma.

Andy began chemotherapy right away. “I knew the most important thing for me was for my kids to know that what happened to their mom was not going to happen to me,” Andy declares.

The Journey for Treatment

Three months before his diagnosis Andy married Patti Evans, a friend he had known for years. “If you get sick, you want Patti on your team,” he says. Patti was caring for her ailing father in Phoenix and was unable to fly to Washington while Andy was undergoing chemotherapy, so instead she secretly called friends and asked them to visit him. “Patti’s just one of those people who is a problem solver. When you’re facing a cancer for which there’s no cure, that’s particularly important,” Andy says.

The chemotherapy was working, and Andy’s cancer was decreasing enough to make him a candidate for a stem cell transplant. On the advice of his physician in Washington, Patti and Andy began to look for a medical center where he would get the transplant. They had consultations with several top medical centers in the U.S., but found their reputations to be different than what he experienced as a patient.

“I can close my eyes and actually see our first visit to Mayo Clinic and my initial interview with Joe — the sense was completely different than what I’d gotten from some of these other places,” Andy emotionally recalls. Joseph R. Mikhael, M.D., is a hematologist at Mayo Clinic in Arizona. He has conducted extensive research on multiple myeloma and is one of the world’s foremost leaders on the disease.

Changing the Outcome

The revolution in multiple myeloma over the past two decades means patients today like Andy are living healthier lives.

Multiple myeloma research has evolved incredibly over the last 10 to 15 years. Today there are new approaches, drugs and transplants that can be used to bring multiple myeloma into remission. In 1997, when Sue Gordon was diagnosed, the use of combining chemotherapy drugs was just in the  experimental stages.

The revolution in multiple myeloma over the past two decades has been fueled by giant leaps in the understanding of its pathogenesis and the development of several novel agents. Today, patients like Andy are living healthier lives, and overall survival has doubled.

Because multiple myeloma is a complex and wide-ranging disorder, it must be managed individually based on multiple interacting disease- and patient-related factors. Mayo Clinic was instrumental in the development of carfilzomib and pomalidomide, two new drugs approved by the U.S. Food and Drug Administration for multiple myeloma in 2012. The last time the federal agency approved a novel myeloma therapy was in 2006. This approval was based primarily on the results of a large Mayo-led clinical trial that took place at multiple centers across the U.S.

Back on the Bike

Andy underwent a combination of high-dose chemotherapy and an autologous stem cell transplant, which means his own stem cells were used. Andy stayed in remission for more than four years.

“I got on with my life. I went back to work and back to riding. I wanted to do something to help find a cure for blood cancers. That’s why I got involved in the Arizona Chapter of the Leukemia and Lymphoma Society,” Andy says. He raised more than $150,000 through cycling fundraisers. Mayo Clinic’s Arizona campus has received grant funds from the Leukemia and Lymphoma Society, which provides research funds to organizations to find cures for blood cancer.

During those four years, multiple myeloma treatments continued to improve. Dr. Mikhael relied on a similar chemotherapy treatment and a second autologous stem cell transplant, putting Andy into a deep remission.

One year after the second transplant, Andy got back on his bike and completed a 100-mile ride around Lake Tahoe. And he’s back to working as an attorney and professor at Arizona State University Sandra Day O’Connor College of Law.

Andy’s children are now 32 and 34. “My greatest joy,” says Andy, as he wipes a tear, “is that I’ve gotten to see our first two grandchildren and will hopefully see many more grandchildren.”

This story originally appeared in the 2017 print edition of Forefront magazine.

Sep 21, 2017 · Game Changers: Five Innovative Tests for Cancer Detection

Finding cancer as early as possible is critical to saving lives. Mayo Clinic is creating a new era in health care with tests that make early and accurate detection of common cancers easy. Many are minimally invasive, convenient, cost-effective and widely available, removing the barriers that prevent people from getting treatment.

  1. Breast cancer can’t hide in dense tissue

Deborah J. Rhodes, M.D., Carrie B. Hruska, Ph.D., Katie N. Hunt, M.D., and Michael K. O’Connor, Ph.D.

Mammography may not be enough to spot breast cancer for about half of all women who are screened. These women have dense breast tissue. They can be helped by a breast imaging technique pioneered at Mayo Clinic that nearly quadruples detection rates of invasive breast cancers in dense breast tissue.

On a mammogram, both dense tissue and tumors appear white. Spotting a tumor in dense tissue is like looking through a frosted glass window. Molecular breast imaging, or MBI, provides a clearer picture.

“MBI can uncover the reservoir of cancers that remain undetected on screening mammography because of masking by dense breast tissue,” says Deborah J. Rhodes, M.D., a Mayo Clinic Breast Clinic physician and a member of the team that developed the supplemental test.

In MBI, a short-lived radioactive tracer is injected into the vein. If tumor cells are present, they absorb the tracer like a sponge and illuminate on the image.

A Mayo Clinic team of physicists, radiologists and internists has spent nearly 15 years developing and evaluating MBI, including three clinical trials with over 5,000 women.

  1. Recurrent prostate cancer lights up

Eugene D. Kwon, M.D., and Val J. Lowe, M.D.

Recurrent prostate cancer lights up Prostate cancer is the most common cancer among men, and about 30 percent of those diagnosed will experience a recurrence. These recurrences can often be difficult for physicians to find.

A Mayo Clinic research team developed an imaging method known as Choline C-11 positron emission tomography, or PET, scan that can find recurrent prostate cancer earlier than other tests.

“It’s a way of looking at the body three-dimensionally so you can see through the body and around the body to find cancer,” says Mayo Clinic radiologist Val J. Lowe, M.D., who helped create the new technology.

Choline C-11 uses a radioactive form of the vitamin choline, which is readily absorbed by cancer cells. The drug is injected into the patient who then has a PET scan.

“Choline C-11 lets us pinpoint at a very early interval where the cancer is returning,” says Mayo Clinic urologist Eugene D. Kwon, M.D., who was part of the team that developed the test.  “Based on what we see in the PET scan, we can more intelligently design the patient’s next therapy.”

In about one-third of men, Choline C-11 PET scanning picks up metastatic lesions that aren’t seen with traditional imaging.

  1. Screen for colorectal cancer at home

David A. Ahlquist, M.D., and his research team collaborated with Exact
Sciences Corp. to develop the test.

Colorectal cancer is the second-leading cancer killer in the U.S.

Yet many people who should get screened skip it. Colonoscopy, the most widely used screening method, is expensive and requires bowel prep, sedation and time off work.

Mayo Clinic researchers co-developed a test, now called Cologuard, that screens for colorectal cancer by measuring tumor DNA in stool. Cologuard is mailed to patients at home and requires only a stool sample, with no bowel preparation, medication or dietary restrictions. A patient mails the sample to a lab for analysis, and results are sent to the prescribing physician. In published studies from the screening setting, this noninvasive, inexpensive test detected 94-100 percent of early, curable-stage colorectal cancers.

Mayo Clinic became the first health care organization to offer Cologuard. Mayo Clinic gastroenterologist David A. Ahlquist, M.D., and his research team collaborated with Exact Sciences Corp. to develop Cologuard.

Among the first 100,000 patients to send in tests, 42 percent had never been screened for colorectal cancer by any approach.

“That’s exactly what we were hoping for — improving screening participation rates should lead to more effective cancer detection at the population level,” Dr. Ahlquist says.

Dr. Ahlquist and Mayo Clinic have a financial interest in Cologuard. Neither Mayo Clinic nor Dr. Ahlquist receives royalties for Cologuard tests ordered for Mayo Clinic patients by Mayo Clinic physicians.

  1. Developing a test for esophageal cancer

Prasad G. Iyer, M.D.

Over four decades, esophageal cancer cases have increased 600 percent in the U.S.

“Compared with all other, more common cancers, incidence of esophageal cancer has skyrocketed,” says Mayo Clinic gastroenterologist Prasad G. Iyer, M.D.

The cancer can be very deadly. A sedated endoscopy at a gastroenterology lab is the recommended screening test today.

Dr. Iyer is collaborating with Exact Sciences Corp. and Mayo Clinic gastroenterologist David A. Ahlquist, M.D., to develop a new screening test that scans for DNA biomarkers of precancerous conditions in the esophagus. The biomarkers are picked up on a capsule sponge that a patient swallows. When the gelatin shell of the capsule dissolves, the released sponge is pulled out, providing cellular samples of the esophagus lining.

The sample can be gathered in a primary care office without the expense and side effects of an endoscopy, Dr. Iyer says. It’s sent to a lab for biomarker analysis.

Early data from studies show very high rates of sensitivity and specificity for predicting the presence of Barrett’s esophagus, a precursor for cancer. The capsule sponge was swallowed by over 90 percent of participants and was safe and well-tolerated. A phase II clinical trial is underway now at Mayo Clinic.

When esophageal cancer is caught early, survival is 80–90 percent.

“That tells the story of why early detection is the best. That’s the whole rationale for early screening,” Dr. Iyer says.

  1. Tampon may do double-duty protection

Jamie N. Bakkum-Gamez, M.D.

Soon, women may be using tampons to screen for the most common gynecologic cancer in the U.S.

An increasing number of women are diagnosed each year with endometrial cancer. Mayo Clinic gynecologic oncologist and surgeon Jamie N. Bakkum-Gamez, M.D., is attempting to change that trend.

“When this cancer is detected early, it has a very high cure rate,” Dr. Bakkum-Gamez says. “But when it’s detected at advanced stages, it’s almost always lethal. And we don’t have a screening test.”

In a 2015 study, Dr. Bakkum-Gamez showed it is possible to detect endometrial cancer using tumor DNA picked up by ordinary tampons. Now her team is working to develop the first early-detection test for endometrial cancer using tampons. This would be a prescribed, self-administered mail-in test, similar to Cologuard.

“We’re keeping the patient at the center of this. We want to make sure this is a test that provides wide access to care,” Dr. Bakkum-Gamez says. Her team is working on a commercially available test.

“This is an exciting time in women’s health, as we’re on the brink of introducing a life-changing test for cancer.”

This story originally appeared in the 2017 print edition of Forefront magazine.

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