Personalized Approach

Bringing Innovation, Discovery and Hope to the Care of Pancreatic Cancer Patients

Weekly MCW Multidisciplinary Pancreatic Cancer Clinical Conference
MCW's Multidisciplinary Pancreatic Cancer Clinical Conference meets weekly. Members include (sitting bottom left, clockwise) Dr. Callisia Clark; Dr. Kathleen Christians; Dr. Murad Aburajab; Dr. Susan Tsai; Dr. Paul Ritch; Dr. Kulwinder Dua; Dr. Beth Erickson; Shannon Lahiff, NP; Dr. William Hall; and (standing, l-r) Dr. Abdul Khan; Dr. Ben George; Dr. Darren Ballard; and Dr. A. Craig Mackinnon, Jr.

John R. Couvillon was on top of the world in early 2014. The successful founder, president and CEO of Atlanta-based Pinnacle Health Group was happily married to Jacqui Fisch, MD, (an obstetrician/gynecologist), father to Alex, 16, and Victoria, 9. The family enjoyed weekend getaways in North Carolina, where they spent quality time together and participated in water sports. A survivor of melanoma in 2007 and noncancerous brain tumors in 2008, Couvillon thought he had overcome the worst curveball fate could throw at him.

Alas, it was not to be. Couvillon began feeling fullness and abdominal discomfort, and in March of 2014, was diagnosed with stage II (operable) pancreatic cancer.

His internist sent Couvillon to see a surgeon at nearby Emory University, but Couvillon's wife did online research into the disease and quickly found world-renowned pancreatic cancer surgeon Douglas Evans, MD, chair and the Donald C. Ausman Family Foundation Professor of Surgery at the Medical College of Wisconsin (MCW). Dr. Evans is based at Froedtert Hospital and holds appointments at Children's Hospital of Wisconsin and the Clement J. Zablocki VA Medical Center.

After joining MCW in 2009, Dr. Evans co-established the translational Pancreatic Cancer Research Program with Susan Tsai, MD, MHS, associate professor of surgery; and Michael Dwinell, PhD, professor of microbiology and immunology, through funding from the Advancing a Healthier Wisconsin Endowment.

The Program's team of physician scientists and researchers undertakes state-of-the-art work to understand the basic biology of the disease to translate this knowledge into new treatments, diagnostic tools and a better outcome for patients.

"Clinical application of research is very important," Dr. Evans says. "Dedication to the patients of today – and importantly, also the patients of tomorrow – is the responsibility of academic medicine."

The translational research program, which now spans many other departments and institutions, is supported by a robust clinical database and tissue bank developed by Dr. Tsai.

The We Care Fund for Medical Innovation and Research also has been instrumental in support of the Pancreatic Cancer Program.

The Couvillons were especially interested in the department of surgery's phase II clinical trial for early-stage pancreatic cancer, which takes a personalized neoadjuvant approach to the treatment of pancreatic cancer.

We Care Fund

Patients with cancer, organ failure and complications from trauma or cardiovascular diseases are searching for two things: hope and a clear plan of treatment.

Bringing hope and innovative treatment plans to patients and their families depends on translating new medical discoveries from the laboratory for use in the operating room, the bedside and the clinic.

The mission of the We Care Fund for Medical Innovation and Research (developed by Arlene Lee and Dr. Evans) is to support researchers and physicians who are creating cutting-edge therapies and clinical programs that benefit patients.

The Fund supports research in the fields of cancer, cardiovascular disease, organ transplantation, fetal concerns and trauma, and its goal is to accelerate the development of those advanced, life-saving solutions by engaging the local community to help bring the best healthcare to Wisconsin.

For more information or to make a gift, please contact Meg Bilicki, director of development, department of surgery, at mbilicki@mcw.edu or (414) 805-5731.

The neoadjuvant approach, pioneered by Dr. Evans, involves chemotherapy, radiation therapy or both given as a first step prior to surgery. "More and more physicians are realizing that this is the best approach – which has led to a huge shift in the paradigm of treatment of pancreas cancer in the past five years," Dr. Evans says.

In June 2016, Drs. Tsai and Evans co-authored an article in JAMA Surgery on "Therapeutic Advances in Localized Pancreatic Cancer," which was based on their efforts at MCW. The physicians concluded that "patients who complete all intended neoadjuvant therapy, including surgery, experience an overall survival benefit that is unmatched by a surgery-first approach."

According to Dr. Tsai, the median survival for patients with operable pancreatic cancer treated with neoadjuvant therapy is 45 months – which is more than double the survival of a surgery-first approach. "A median survival of 45 months is unheard of," she explains. "There are very few institutions in the US that have published this type of data." These results strongly suggested that MCW physicians were on the right track: treatment sequencing matters. The pancreatic cancer team of physicians at MCW then hypothesized that patient outcomes could be further improved by personalizing their neoadjuvant approach to individual patients.

Before the clinical trial could be designed, however, the investigators had to clear a major scientific hurdle. No technique existed to obtain the amount of tissue from a living patient needed to analyze the genes in a pancreatic cancer tumor. A diverse team of MCW specialists, under the leadership of Kulwinder Dua, MD; Abdul Khan, MD; and A. Craig Mackinnon, Jr., MD, PhD, capitalized on a new, safe and minimally invasive procedure which uses endoscopic ultrasound to guide a needle into the tumor. Using the biopsy material obtained in this way, the pancreatic cancer research team creates genetic profiles of each patient's tumor to determine the type of chemotherapy most likely to be effective for an individual patient.

To enhance the collection of research specimens, Dr. Tsai developed the Pancreatic Cancer Biorepository, which includes a tissue bank with blood and tissue gathered at multiple stages of pancreatic cancer treatment. MCW is one of only a few institutions with this sampling procedure – which gives scientists the ability to assess the disease over time.

For the clinical trial, physicians identified six specific molecular targets that are predictive of chemosensitivity to agents commonly used to treat solid tumors (pancreas cancer and other diseases). As part of the trial, investigators analyze each patient's tumor for these molecular target(s) and subsequently individualize the neoadjuvant treatment based on the tumor's molecular profile. Those patients who demonstrate stable/responding disease as assessed by biochemical, clinical and radiologic measures are then taken to surgery. This unique personalized medicine trial is the first of its kind for operable pancreatic cancer.

The research team, which includes medical oncologists Paul Ritch, MD; Ben George, MD; and James Thomas, MD, PhD; radiation oncologists Beth Erickson, MD; and William Hall, MD; surgical oncologists Kathleen Christians, MD; Callisia Clarke, MD; and Drs. Tsai and Evans; advanced practice providers; and research nurses, meets each Friday at 6:30 a.m. to review the progress of all patients on the trial.

This is followed at 7 a.m. by the weekly Multidisciplinary Pancreatic Cancer Clinical Conference, which is supported by dedicated faculty from the departments of radiology and pathology, and the division of gastroenterology (department of medicine).

It truly "takes a village" to bring innovation, discovery and hope for a better tomorrow to the care of the pancreatic cancer patient.

Begun in late 2011, the clinical trial recently closed after enrolling 130 patients.

Ten individuals are still receiving the assigned neoadjuvant treatment and have not yet been evaluated for surgery.

Pancreatic cancer stats | Source: American Cancer Society

"There has been a huge push for precision medicine, especially in oncology," notes Dr. Tsai. Physicians involved in the clinical trial are looking at protein expression from samples that are taken directly from the tumor from each patient. "We are transforming conventional chemotherapy into a more targeted approach and view our efforts as 'personalized medicine' rather than 'precision medicine' – as each patient may receive a different drug therapy. If we can match the patient to the treatment a little bit better, we can improve how many people complete all intended therapy including surgery – and importantly, decrease the number who develop metastatic disease."

Dr. Tsai shares that patients such as John Couvillon are looking for personalized therapies, especially in cancer – so it makes sense to try to tailor the therapy specifically to the tumor. "Historically, the efficacy of standard therapies for pancreas cancer were quite limited, so everyone is eager to participate in clinical trials," she adds.

In MCW's pancreatic cancer clinical trial, a needle biopsy is done on each patient's tumor at time of the diagnostic endoscopy. Tissue is taken to MCW's Clinical Translational Research Core Laboratory, where Dr. Mackinnon, associate professor of pathology and director of the lab, does the staining and interpretation. The staining is fairly technical, but turnaround time averages one week.

"In most other centers, the median time from diagnosis to treatment is three to four weeks, so we actually are ahead of the game," Dr. Tsai notes. “Based on the staining, MCW physicians utilize different chemotherapy regimens, many of which are already on the market. And since the drug discovery time period can be 10-13 years, taking advantage of drugs that we already have available and know to be efficacious seemed to make sense."

As a result of the clinical trial, MCW's Pancreatic Cancer Biorepository has grown to more than 450 specimens. Collected at various stages of treatment, these human specimens (from the patient's tumor as well as DNA and proteins from blood) provide valuable insights into how pancreatic cancer develops and how it can be treated.

After meeting with the team at MCW, Couvillon enrolled in the clinical trial and received between two and three months of chemotherapy in Atlanta, based on his individualized protocol prescribed by Dr. Ritch and the MCW physician team. "My wife and I felt great about my being under the care of Dr. Evans. We knew I didn't need to go elsewhere for my treatment," Couvillon recalls.

On June 16, 2014, he underwent a pancreaticoduodenectomy performed by Dr. Evans at Froedtert Hospital. Known as the "Whipple procedure," the surgery involved removing the head of the pancreas (the site of Couvillon's tumor), his duodenum (the first part of the small intestine), gallbladder, part of the common bile duct, and more than 30 nearby lymph nodes.

Couvillon remained hospitalized for five days, and spent another five days recuperating at a nearby hotel. "After surgery, Dr. Evans gives you a purple card (purple is the color of pancreatic cancer awareness), which is a plethora of knowledge," Couvillon shares. "Shannon Lahiff, NP, and Beth Krzywda, NP, were very helpful to work with after surgery. Your body goes into shock. It took me a few months before I could eat a meal similar to before diagnosis. I lost about 20 pounds and learned that I needed to eat small meals often. The entire support staff was absolutely amazing. I can’t say enough about them."

Pancreatic cancer is the third-leading cause of cancer deaths in the US. More than 53,000 individuals will be diagnosed with the disease this year; southeastern Wisconsin has an unusually high incidence, which is something the research team here is examining.

John R. CouvillonCouvillon's gratitude for surviving this relentless disease, and his desire to provide hope to others suffering with it, prompted him to establish Destroy Pancreatic Cancer, a non-profit organization to fund and advance research and clinical trials that lead to earlier detection and improved treatment options.

As a result of this collaboration, Destroy Pancreatic Cancer has proposed a series of innovative clinical trials (to begin in October 2017) to advance care for pancreatic cancer patients by bringing an additional cutting-edge combination drug treatment protocol to patients and to develop a center of excellence for pancreatic cancer care in Atlanta. The clinical trials will be coordinated by Dr. Evans; Daniel D. Von Hoff, MD, physician-in-chief and director of translational research at the Translational Genomics Research Institute (TGen) in Phoenix, Arizona; and W. Perry Ballard, III, MD, co-founder of Piedmont Cancer Institute (PCI) in Atlanta.

The organization has pledged significant support to pay expenses outside the standard of care such as research nurses, correlative laboratory studies, pre-treatment tumor biopsies, tumor sequencing and genome analysis. "I also want to fund a surgical clinical trial," Couvillon remarks.

"Dr. Evans is the doctor every pancreatic cancer patient deserves, and it is his personal mission to train and share his knowledge with medical professionals who have dedicated their careers to destroying pancreatic cancer," Couvillon says.

For the two-and-one-half years following his surgery, Couvillon's scans, performed every three months, were clean. In January 2017, however, a scan showed a return of the cancer – and he immediately began another chemotherapy protocol. He is doing well, staying positive and determined to continue his quest to destroy pancreatic cancer.

The entire MCW pancreatic cancer team is feeling good about the progress of the clinical trial – the results of which are expected to be published by the end of 2017. "We are hopeful for a positive outcome, as things look very encouraging compared to conventional therapies," Dr. Tsai says.

She shares that a follow-up trial, which builds upon the molecular profiling of the trial just completed, currently is going through MCW's Institutional Review Board (which reviews research protocols and related materials to ensure that diseases such as pancreatic cancer receive cutting-edge innovations as quickly and safely as possible).

"What’s unique about the next trial is it's more of an adaptive trial to see very quickly if the drug therapy is working, and if not, to switch to another therapy right away," Dr. Tsai notes. This next clinical trial, when approved, will involve approximately 150 patients over a six-year span.

There are many reasons for physician scientists and researchers to tackle this devastating disease, according to Dr. Tsai. "When you take care of pancreas cancer patients, it's pretty compelling to participate in research. There is a real need for this kind of meaningful translational research, especially when you get to know the patient and her/his family. We must make progress for the patients of tomorrow. In 30 years we hadn't made any significant improvements in overall survival, except for the past six to seven years. We're on the cusp of many great advances, and it's an exciting time because the awareness of pancreas cancer is improving and we're seeing more and more survivors – which gives us momentum to make some change in the disease."

John Couvillon couldn't agree more – and is determined to help move progress along at the fastest rate possible.

– Sara L. Wilkins
 

MCW Magazine: Clinical story MCW Magazine: Discovery story MCW Magazine: Philanthropy story
CLINICAL | DISCOVERY | PHILANTHROPY

Postscript:

As this article went to print, John Couvillon died suddenly and unexpectedly on a Saturday morning after an uneventful week of work, much of which was spent further developing his foundation, Destroy Pancreatic Cancer.

While his sudden death remains a mystery, his resolve to make a difference for future patients with pancreatic cancer leaves no question in the hearts and minds of family, friends, physicians and scientists who will ensure that Destroy Pancreatic Cancer leaves a legacy of life-saving discoveries for a man whose goodness and generosity may change the landscape of cancer care.

– Dr. Douglas Evans

Medical College of Wisconsin…8701 Watertown Plank Rd., Milwaukee, WI 53226
(414) 955-4725  |  Fax: (414) 955-6699  |  MCWmagazine@mcw.edu

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