How Our Research Improves Cancer Treatments

Miles to Go

Clinical research has improved the outlook for most kids with cancer. Here’s why the future promises to be even better.

Alyssa Zoll, 11, still undergoes physical therapy to learn to walk with the titanium and cobalt implant that replaced the cancerous part of her femur.

Alyssa Zoll, 11, still undergoes physical therapy to learn to walk with the titanium and cobalt implant that replaced the cancerous part of her femur. Dr. Doug Hawkins, her cancer specialist, and Dr. Antoinette Lindberg, her orthopedic surgeon, check her gait.

It seemed like a stubborn infection in her hip. But when several rounds of antibiotics and bed rest couldn’t make the intense, recurring pain in 11-year-old Alyssa Zoll’s femur go away, an MRI and biopsy explained why: Alyssa had Ewing sarcoma, a rare bone cancer that mainly affects children and adolescents.

The standard treatment plan was clear and proven to be about 75% effective – 14 rounds of chemotherapy delivered every other week and surgery to replace two-thirds of Alyssa’s femur with a titanium and cobalt rod. Bone cancer specialist Dr. Doug Hawkins introduced another option: a clinical trial studying whether adding an additional chemotherapy medicine would improve the chances of a cure.

“We decided to go for it,” recalls mom Michella Zoll.

Small steps = big change

Over the past 40 years, a cancer diagnosis has gone from a death sentence to a survivable illness for nearly 80% of all children under age 15. Credit for this incredible progress belongs to clinical trials – research studies involving people that systematically test new ways to diagnose and treat illnesses. Since the 1990s, most trials study small tweaks to the standard best practice – like adding or combining different medicines, changing the dosage schedule or altering the amount of medicine. If the changes work better, they become part of the standard practice and the next promising idea gets compared to that.

Though rare, cancer is the leading cause of death by disease among U.S. children 14 and younger.

Alyssa’s clinical trial features several innovations with roots right here at Seattle Children’s. Our pilot study with Children’s Hospital of Philadelphia from 1991 to 1995 showed it was safe to shorten the medication schedule from every 3 weeks to every 2 weeks. A larger national study then showed that the shortened schedule improved the chances of being cured by 11% without increasing side effects. Getting chemo every 2 weeks then became the standard treatment for all children with Ewing sarcoma.

Giving a different medication to help white blood counts recover after chemotherapy is another improvement born here. Patients used to get one shot a day for 7 to 10 days after each round of chemo. Seattle Children’s helped show that a different medicine – one that could be injected just once after each round of chemo – was just as effective. While this advance doesn’t impact long-term survival, it improves the patient’s quality of life during treatment.

And studies in the early 1990s at the University of Washington and Seattle Children’s suggested that positron emission tomography (PET) scans (which measure how active cells are) are a powerful predictor of whether the cancer will relapse. The trial Alyssa is in will compare patients’ pre-treatment PET scans to a second scan taken about halfway through treatment to test whether the predictive power holds true across a broader patient population.

A game-changing shift

Leukemia survival rates

This graph (showing the vast improvements in leukemia survival rates since 1956) is illustrative of better outcomes for all cancers thanks to clinical research studies.

Doctors and researchers at Seattle Children’s have long been at the forefront of figuring out better ways to treat many forms of childhood cancer. Through leadership positions in national and international cancer-fighting coalitions (like the Children’s Oncology Group), our experts help set the worldwide agenda for pediatric cancer research. During the past four decades, these collaborative groups have translated scientific hypotheses into incremental improvements that make life better for kids and teens with cancer.

Today, a seismic shift in how improvements to cancer treatment will be found is underway – thanks to new knowledge of cell biology and genomics. These developments are expected to result in more personalized, more effective and less toxic treatments.

“Right now we say ‘you have this type of cancer, we’ll give you this treatment,’” says Hawkins. “In the future we’ll say, ‘your cancer has this specific mutation, so we’re going to give you this specific medicine.’ Advances in our understanding allow us to target a specific protein or process, rather than just damage a lot of cells in an effort to stop the cancer. Our goal is to deliver this knowledge to our patients.”

Biology of brain tumors

Drs. Leary and Cole

Drs. Sarah Leary (left) and Bonnie Cole found that certain proteins expressed by brain tumor cells were the best predictor of whether a child’s cancer would relapse or be cured. Mentorship from Drs. Doug Hawkins, Julie Park and Russ Geyer sharpen her work, says Leary. “Having any one of them here would be amazing. Having them all here is incredible.”

Brain tumors are the most common solid tumor in children. Dr. Sarah Leary wants to know why most kids with brain cancer respond well to current treatments but others don’t.

“It may sound great to say we’re curing 70% to 90% of the kids, depending on their type of cancer. But if you’re not one of those kids, it’s not so great. That's who keeps me up at night,” she says.

To learn more, Leary partnered with Seattle Children’s pathologist Dr. Bonnie Cole to analyze hundreds of samples of brain tumor tissue donated by former patients. They found that certain proteins expressed by brain tumor cells were the best predictor of whether a patient’s cancer would be cured or relapse.

Leary now leads several clinical trials aimed at turning that realization into better treatments for the 30% of patients whose brain cancer doesn’t respond well to the current best standard treatments. Some of the trials are testing whether existing FDA-approved drugs designed to act on those proteins in other cancers in adults will work for children with brain tumors. She is also leading studies to develop new drugs.

“It will be a decade before we know if the studies we’re doing today will make a difference,” Leary notes. “But if we’re smart enough, we can beat this.”

Body, heal thyself

Drs. Jensen and Gardner

“I came to Seattle for my oncology fellowship because Seattle had a group of researchers looking at cancer immunotherapy and I thought using one’s own immune system to recognize and fight cancer cells was an elegant idea,” says Dr. Rebecca Gardner, pictured with Dr. Mike Jensen.

The dream of curing cancer without chemotherapy and radiation took a leap forward in 2013 as Seattle Children’s work to use reprogrammed T cells to treat relapsed acute lymphoblastic leukemia (ALL) transitioned from treating mice to helping people.

In this new field, called cancer immunotherapy, a patient’s own T cells are genetically modified to recognize cancer cells and attack them – just as unmodified T cells attack viral infections in healthy people. The hope is to reduce, and possibly even eliminate, the need for chemotherapy and radiation and their debilitating lifelong effects.

“We’re just a few patients in, but we can already tell that we’re onto something sustainable,” notes Dr. Rebecca Gardner, who leads the cancer immunotherapy trial. “It doesn’t take much to see that the therapies we currently give kids aren’t benign – and fewer than 40% of people with relapsed ALL survive. It’s imperative that we find new paths to a cure.”

Milton 145

“At first, I cried when they told me my cancer came back the second time. Then, I laughed because I knew there weren’t treatments for people who relapsed twice. I started wondering what I’d do with the rest of my life. Then Dr. Gardner asked me if I wanted to be the second patient in her trial,” recalls Milton Wright III, 20, now in remission after receiving an infusion of his reprogrammed T cells nearly a year ago. “My story isn’t any different than any other cancer patient. We’re all fighting for our lives and we all have a story to tell.”

Unlike typical cancer treatments, T-cell therapy is a living therapy with the potential to remain in the patient’s system. Once the modified T cells are infused into the patient, they take root, divide and make more T cells. The hope is that the modified T cells will remain at the ready to defend the body if the cancer tries to come back.

The time is now

Cancer is the No. 1 cause of death by disease among U.S. children, yet only 3¢ ($0.03) of every National Institutes of Health (NIH) funding dollar goes to childhood cancer research. And because childhood cancer is so rare, the return on investment doesn’t attract funding from pharmaceutical companies.

“We’re at an incredible juncture where we have new ways to understand cancer’s biology and deliver personalized medicines to patients, yet the national infrastructure that is essential to funding clinical trials is being chipped away due to reductions in federal support for research,” notes Hawkins.

Currently, government funding covers about half the cost of having a patient participate in a research study. At Seattle Children’s, donors and support from the hospital make up the rest.

“I’ve been a physician for 24 years. I've seen lots of children and families suffering. I've seen treatments that don’t work and treatments that are too toxic. And I’ve seen it change,” says Hawkins. “We’re so close to figuring out ways to deliver better treatments to our patients. Clinical trials are our best hope.”

Motivated to Make Change

She was a typical eighth grader. Then,in March 2013, Kat Tiscornia found out she was one of only 200 children and adolescents diagnosed each year with a rare form of bone cancer known as Ewing sarcoma.

Feeling no kid deserves to face the challenges of sarcoma, Kat decided to raise money to support sarcoma research spearheaded by her doctor, Dr. Doug Hawkins. Engaging her community and speaking at numerous fundraisers helped Kat's Crew raise more than $168,000 while she underwent 9 months of chemotherapy and maintained an A average.

“I spent a lot of time thinking about why cancer happened to me. The only answer that makes sense is so that I could make a difference for kids like me who get sick,” Kat reflects. “I learned that research is the key to improving cancer treatments, so I am raising money for sarcoma research because I want to make treatments shorter, more effective and take less of a toll on the body.”

Learn more about Kat.

Published in Connection magazine, September 2014