Just a toddler, Madison Pagel already faced a crossroads.
She had a brain tumor that continued to grow despite multiple rounds of chemo. Cancer grew in her spine and spinal fluid.
Her parents were advised to seek hospice care.
Unless what? They could try a clinical trial for incurable pediatric cancers. The study, led by a physician at Spectrum Health Helen DeVos Children’s Hospital, analyzes tumors to choose drugs that target their specific molecular makeup.
Two paths lay before the family that day in September 2013.
One led to death. “No. No. Nope, nope,” was all her mother could say.
The other offered a wisp of hope—but also continued medical treatment with no guarantee of success. Maddie, 2½ years old, had spent most of the past year in the hospital, either to receive chemo or to cope with the side effects.
If her time was limited, her parents wanted the best quality of life possible for the remainder of her days.
Their decision: Try the clinical trial, but with one condition. Maddie would receive only oral drugs—ones she could take at their home in Kentwood, Michigan.
A full life
Fast-forward two years. Maddie runs across the living room to her dad. He scoops her up, turns her upside down and tickles her. Maddie’s laugh rings out like a series of chimes.
All I remember him saying is, “It’s rare.’ And possibly, ‘We might lose her, but we will do everything that we can.’”
She and her 3-year-old sister, Avah, model princess costumes. Maddie wears the Snow White dress, a black flower headband decorating her long, brown hair. Avah wears Elsa’s shimmery blue dress.
Maddie plops in a chair, and her 1-year-old brother, Hunter, climbs on her lap.
This is the full life of a 5-year-old cancer warrior. She still takes medication every day. But she also keeps pace with the antics of friends and siblings.
“We weren’t even sure she would make it to Christmas,” said her oncologist, Albert Cornelius, MD. “And now here she is, almost two and a half years later, doing great, going to school. It is very exciting.”
In Madison’s heartwarming progress, doctors see hope for the larger fight against cancer.
“We are starting to figure things out,” Dr. Cornelius said. “It doesn’t mean this combination of medicines is going to work for every tumor. But it certainly is giving us insight into this tumor and to maybe how we need to treat cancer in the future.”
A change overnight
Maddie’s parents, Tracy and Frank Pagel, said the first sign of cancer surfaced the day after their daughter’s 4-month wellness checkup. All seemed fine at the doctor’s office.
But the next evening, she began to vomit “excessively,” Tracy said. “I yelled at Frank, ‘Get her car seat. We are heading into the ER.’”
A CT scan revealed Maddie had a mass the size of a golf ball in her brain. An ambulance transferred her to Helen DeVos Children’s Hospital.
On Jan. 7, 2011, a surgeon removed the mass. It measured more than 1.5 inches across.
“In her tiny little brain, that was huge,” Tracy said.
Four days later, the Pagels heard the news they dreaded: It was cancer. Maddie had an extremely rare brain tumor called choroid plexus carcinoma.
“All I remember is him saying is, ‘It’s rare.’ And possibly, ‘We might lose her, but we will do everything that we can,’” Tracy said.
She and Frank went to the waiting room where family had gathered. And Tracy broke down.
“I didn’t even know what to think,” she said.
Maddie began chemotherapy the next day. By the time she reached her first birthday, she had undergone 11 cycles of chemo.
The cancer went into remission. For nine fleeting months, the Pagels hoped it was gone for good. But then it came back.
Her doctors tried three more combinations of chemotherapy. The last one required Maddie to spend alternating weeks at the hospital and home.
The cancer came back again. Maddie was 2½.
“Now it had spread,” Dr. Cornelius said.
Cancer crept along in her brain, spine and spinal fluid. A tumor pressed on the nerves in her back and caused pain in her leg.
The DNA breakdown
That is when the Pagels opted to try the clinical trial.
The research led by Giselle Sholler, MD, involves precision—or personalized—medicine. The doctors took a biopsy of Maddie’s tumor and analyzed its DNA for mutations. They also compared it to her normal DNA.
“Nobody’s perfect. We all have mutations,” Dr. Sholler said. “If you just look at the tumor’s DNA mutations, you don’t necessarily know which ones are causing the cancer. If you compare it to her normal DNA, what’s different is really what caused the cancer.”
The analysis also looked at the RNA sequencing, which indicates which genes are active.
The doctors presented the results at an online meeting of the tumor board—physicians and scientists from a research consortium encompassing 25 hospitals and universities.
“We were able to put together a combination of four medicines that target the pathways—not just one pathway, but multiple pathways that were driving her tumor,” Dr. Cornelius said.
Several drugs are used at the same time because a tumor can develop resistance to a single drug, Dr. Sholler said. By attacking on multiple fronts, doctors believe they can close off the tumor’s escape paths.
And the medications chosen had minimal side effects. That followed not only the parents’ wishes, but also the clinical trial’s goals—the researchers aim for effective, less toxic therapies.
The drugs included:
Thalidomide—the medication was once given to pregnant women for nausea and later found to cause birth defects.
“It is being used now in brain tumors as a way of cutting off or reducing the blood supply to the tumor,” Dr. Cornelius said. “We are taking the bad side effect of this drug and actually using it to fight tumors.”
While pregnant with Hunter, Tracy could not even touch the medication because of its association with birth defects. Frank handled that task.
Sunitinib—a targeted agent usually used in adult kidney cancer.
Sirolimus—a drug that prevents graft rejection in organ transplants. It is believed to prevent resistance to cancer treatments.
Vorinistat—an agent used to target cancer that works differently than chemo.
‘It has shrunk dramatically’
“After just one month, there was no tumor in her spinal fluid,” Dr. Cornelius said. “And then after six months, the tumor in her spine was gone.”
At a recent checkup, the news got even better. He showed the Pagels four images from MRI scans taken during the past 2½ years. The small white circle near the center of her brain appeared noticeably smaller in each one.
The brain tumor is now 2 to 3 millimeters—down from 8 millimeters originally.
“It has shrunk dramatically,” Dr. Cornelius said.
Do we understand everything? Not yet. Do we cure everybody with cancer? Not yet. But we are getting closer every day.
Initially, Maddie had nausea and thinning hair from the treatment. But overall, she adjusted well, Tracy said. She began pre-kindergarten in the fall and loves school.
A hospitalization with pneumonia in December was her first inpatient stay in two years.
“The clinical trial is way better than any chemo she’s been on,” Tracy said. “It’s really been a blessing.”
Over time, her doctors dropped two of the medications—Vorinistat and Sunitinib. Still, Maddie did well.
“I think right now the tricky thing is to know when to stop,” Dr. Cornelius said. “She’s doing so well. Is she cured? Is she not? Is there a point where we could actually stop?”
That is a question he couldn’t even contemplate in September 2013.
Dr. Sholler explained Maddie’s cancer is particularly challenging because she has a mutation in the P53 gene—the gene that puts the brakes on tumor growth. The prognosis is poor when that mutation is present in choroid plexus carcinoma.
Will Maddie be the first long-term survivor? Her family and doctors hope this is the case. “It’s pretty amazing how far out she is,” Dr. Sholler said.
And the fact that Maddie has reached this point shows the value of applying research developments quickly to patient care, Dr. Cornelius said.
“Do we understand everything? Not yet. Do we cure everybody with cancer? Not yet,” he said. “But we are getting closer every day.”
Dr. Sholler agreed: “One child at a time.”
Hope and fear
One downside to Madison’s unique journey is the uncertainty about what will come next.
“I just wish we could wake up one day and it’s all done,” Tracy said. “It’s a very hard thing. We don’t know what this cancer will do. We still live just day by day.”
While the stress of her illness is difficult, her parents are inspired by Maddie, a little girl who stays playful and happy through all the tests and treatments. It helps keep life in perspective.
“She’s amazing,” Frank said. “She is stronger than anyone I know—by far. You hear people complaining about how bad their day is and how stressed out they are. Come on. What this kid goes through—it changes you.”
And there are plenty of moments like this one, during Maddie’s recent visit for blood work. She came into the exam room and happily showed her sparkly purple hat to the nurse.
But when it was time to lie on the bed, a worried frown crossed her face. She resisted.
With some coaxing, Maddie slowly lay back. And then she turned to look at her mother.
“I love you, Mommy,” she said.
“I love you, too.”
What a wonderful story to read! My little brother had a choroid plexus carcinoma at 8 months old. Nearly 29 years later and he is still healthy and cancer free!
Wonderful! Thank you for sharing! 🙂
Wow! CPC is a very difficult presentation today. That he beat it 29 years ago is just stunning. I’m sure Maddie’s mom would love to hear his story. Hope is one of the best drugs. Maddie has a Facebook page. Not sure if they allow URL posts on here but it is an easy search.
Thanks Eddie! Appreciate your Health Beat readership and for sharing another perspective. 🙂