Mother’s clinical trial inspires her daughter

Research Day speaker Celine Ryan offered a unique perspective on participating in a cancer clinical trial, which led her daughter, Holly, to pursue an MD-PhD at UF

Trainees, scholars, students, and pilot award recipients who recently presented their work at the UF Clinical and Translational Science Institute, or CTSI, and M.D.-Ph.D. Training Program’s Research Day heard a unique perspective from a keynote speaker who’s been featured in the New York Times and the New England Journal of Medicine — and who owes her life to research.

The speaker, Celine Ryan, participated in a clinical trial that left her cancer-free despite a grim diagnosis. Celine Ryan is also the mother of second-year M.D.-Ph.D. student Holly Ryan.

“This is a day to celebrate scholars, trainees, pilot winners and the M.D.-Ph.D. students we’ve recently brought into the CTSI fold,” said CTSI director David R. Nelson, M.D., who also serves as UF Health president and UF senior vice president for health affairs. “They’re presenting the research they’ve done with the help of their teachers and mentors. One day, they’ll have the opportunity to see their research help people who walk into this hospital, people like Celine Ryan.

“With the help of new CTSI programs such as the drug discovery and learning health system,’’ he said, “and other new programs on the horizon, that’s the vision: translating the research generated in this room into improved health for the community and the nation.”

Celine Ryan told her inspirational story of self-advocacy from cancer diagnosis to clinical trial to recovery, and answered questions on a panel with her husband, Patrick Ryan, and Holly Ryan.

Celine Ryan was diagnosed with Stage 3 colon cancer at age 47 in 2013. A busy mother of five, she continued to homeschool three of her five children while recovering from surgery and undergoing chemotherapy treatments near her home in Michigan.

“I was 17,” said Holly Ryan. “I had just come back from college orientation and had all of this excitement brimming, wanting to tell my parents all about my day. My dad said “cancer,” and it wasn’t what I had expected to hear.”

The Ryans didn’t tell their children much about their mother’s illness. Life had to keep going.

“We really tried to shield the kids,” Celine Ryan said. “We wanted to keep their lives as normal as possible. We didn’t want them sitting at home worrying about mom.”

Both engineers, the Ryans kept Celine’s medical records and scans, and plotted the tumors on their home computer.

After chemotherapy, the cancer appeared to be in remission. But a follow-up scan showed the tumors had grown.

“I wanted to recover from surgery, get chemotherapy and be cured,” Celine Ryan said. “That is not how the story played out.”

The diagnosis was terminal. The oncologist wanted to do chemotherapy. Ryan wanted to do a clinical trial. She had read about the latest research in immunotherapy and self-referred to the National Institutes of Health.

Researchers were using cells called tumor-infiltrating lymphocytes, or TILs, to target the type of mutation Ryan had, KRAS, one of the most common mutations in colon and pancreatic cancers. In the trial, researchers extracted the patients’ own TILs, multiplied them in the lab, then infused the cells back into patients’ bodies.

“I loved the idea that my own body had the ability to kill cancer cells; we just needed to harness it in some way,” Ryan said. “It made sense.”

She was eventually accepted into the trial. Knowing that this time her ordeal had a larger purpose – advancing science and helping other patients – kept Ryan focused during seven days of conditional chemotherapy.

“This time it was bigger than just prolonging my life,” she said.

She lost her hair, became nauseous and fatigued, and couldn’t sleep. She spent 24 days in the NIH hospital, lonely because she had asked her family not to visit her lest they bring germs into the presence of her weakened immune system.

Doctors infused 148 billion of her own TIL cells into her body, which were reactive against the mutation in her tumors.

“They were very excited,” Ryan said. “They had never had a patient like this before. What if they could cure KRAS? I just wanted to live. I was happy that they were excited, though.”

Every scan after the cell infusion showed a favorable response. She was discharged. Every month at her follow-up appointments, the tumors kept shrinking.

In January 2016, she was declared a “partial responder.” However, one tumor that had initially responded looked active. They decided on a full lung lobectomy, and Celine was the first person to be declared cancer free after TIL therapy followed by a lung lobectomy.

Still a college student at the time, Holly Ryan had started thinking about a medical career. The medical Fellow working with her mother offered to let her shadow him at the NIH hospital for a day, and her interest in research was piqued.

“When I went home that day I didn’t want to leave,” Holly Ryan said. “I just knew I wanted to be a research physician.”

She applied to the M.D.-Ph.D. training program at UF and is in her second year with a focus on biomedical engineering, mentored by Chelsey Simmons, Ph.D., an assistant professor in the department of mechanical and aerospace engineering; and Keith March, M.D., Ph.D., a professor of medicine in the UF division of cardiology. Thomas A. Pearson, M.D., Ph.D., M.P.H., directs the M.D.-Ph.D. and CTSI Translational Workforce Development programs.

The findings were published in the New England Journal of Medicine, and the reporters started calling.

Celine and Patrick Ryan wanted their story to be told. They had learned about research trials from other patients who had told their stories, and now they hoped their story might inspire others. And they have. They continue to tell their story in articles, and at events like CTSI Research Day around the country.

“As fun and as great as all the articles were, something else happened that was quite joyful,” Celine said. “My daughter Holly posted on Facebook that something had happened in her immunology class that day. The professor put up a slide of a woman whose case was published in the New England Journal of Medicine. Holly said, “I know those lungs! Those are my mom’s lungs!”

The Ryans had advice for the future doctors and researchers in the audience. Patrick Ryan urged them to put themselves in the shoes of their patients, having heard Celine’s story. Consider what would be important to her as a mother and as a patient who had received a terminal diagnosis. Would they tell patients about clinical trials? On one hand, a trial could shorten their patient’s life but, on the other hand, it had the potential to save their life? Or would they instead recommend chemotherapy treatment that had only the possible upside of extending life by a few months for someone with a terminal diagnosis?

“As doctors, you need to listen to your patients and learn what their risk tolerance is,” Patrick Ryan said. “Would they take the chance of raising their children rather than no chance at all?”

Patients need to be completely informed about their disease process and the options available to them, Holly Ryan said.

“My mom knew what kind of quality of life she wanted to have for herself,” she said. “Having that knowledge as a medical student was important for me to realize how I need to treat patients when I am a doctor one day.”

Watch the short video interviews with the Ryan family below, or watch the entire recorded presentations and Q& A session from the CTSI & MD-PhD Program Research Day here.

Poster Presenters and Titles from the 2019 CTSI/MD-PhD Program Research Day

MD-PhD Program Presentations

Trainee and Scholar Presentations

KL2 Scholars

TL1 Team Trainees

Poster Title: A TL1 team approach to multiplexed immunoaffinity capture of osteosarcoma cells in microfluidic devices

Poster Title: A TL1 team approach to validating SGCD (rs2116737) genotype-discrimination interaction as a determinant of blood pressure variation in the Jackson Heart Study

Poster Title: A TL1 team approach to identifying neurophysiological signatures of motivaitonal disorders in Parkinson’s disease

Poster Title: A TL1 team approach to cancer cell to antigen presenting cell conversion in 3D printed models

Poster Title: A TL1 team approach to personalizing donor human milk for the preterm infant

Poster Title: A TL1 team approach to examine rural tobacco users’ barriers to participating in research

Poster Title: A TL1 team approach to clinician perspectives on hoarding disorder

Poster Title: A TL1 team approach to CNS-localized delivery of neurotrophic factors for treatment of Parkinson’s disease

Pilot Awardee Presentations