Advances in Pediatric Cancer Treatment

‘It’s a very exciting time in cancer therapy and that extends to the care of children with cancer,” says doctor

By Deborah Jeanne Sergeant

In 1970, fewer than 5% of pediatric cancer patients would be cancer-free five years later. Today, 81% of childhood cancer cases are.

In addition to raising that number to 100%, Holly Dutcher, executive director of CURE Childhood Cancer Association in Rochester, wants to see more funding to improve the quality of life for children undergoing cancer treatments.

“What isn’t being considered is the toll these therapies take on the children,” she said. “Children are constantly growing, whether it is mentally, emotionally or physically. The experience of childhood cancer, both from a medical standpoint and beyond, affects children tremendously. There are late effects that children suffer as a result of their treatment.”

She listed hearing loss, cognitive issues, learning difficulties, social isolation, among many more.

“If these children are lucky enough to survive cancer, considering the toll the current therapies take on their organs, mental health, cognitive skills, there is always room for improvement,” Dutcher said.

A few emerging treatments show promise for beating cancer while reducing the long-term health implications of traditional treatments like chemotherapy and radiation.

“In general, it’s a very exciting time in cancer therapy and that extends to the care of children with cancer,” said physician Kara Kelly, chairwoman of the Roswell Park Oishei Children’s Cancer and Blood Disorders Program in Buffalo. Kelly is also a professor of pediatrics at University at Buffalo’s Jacobs School. “We’re very fortunate to offer many of these innovative therapies in Buffalo with our collaborations with Kaleida, Roswell and UB Pediatrics.”

One of the latest ways to treat childhood cancer includes immunotherapy. While chemotherapy and radiation are often very effective in treating many kinds of childhood cancer, the side effects, both short-term and long-term, can devastate children’s health: raised risk of second cancers, life-threatening cardiovascular disease, lung complications, and kidney and liver damage.

Immunotherapy is like a sharpshooter, targeting the cancer while sparing the healthy cells. One kind of immunotherapy is chimeric antigen receptor T-cell or CAR T-cell therapy. This treatment is now FDA approved for children whose B-cell acute lymphoblastic leukemia has not responded to conventional therapy.

Medical providers collect T-cells from the patient, filter their blood and modify those T-cells so that home in on receptors on the surface of the cancer cells. The cells are reinfused back into the patient to clear out the cancerous cells.

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Fewer than 10% of the patients receiving CAR T-cell therapy would have survived without it. But receiving the therapy spares 65% to 70% of patients.

“Immune therapy requires specialized care,” Kelly said. “In a way, the analogy is like what’s happening with COVID-19. Some get sicker form the immune response than the virus. T-cell therapy can cause children to get very sick until that passes.”

While children receive CAR T-cell therapy, they can mount a serious immune response, like they have a very serious infection. Some require a ventilator or experience neurologic toxicity with seizures. The therapy increases the risk of certain types of infection, but these are typically manageable.

Because these are still recent therapies, researchers have only eight or so years of follow-up to tell them about patient longevity. More time is needed to track and monitor patients so researchers can better understand the long-term effects.

“Building on this success in leukemia, we and others are now using this T-cell approach in other types of diseases and using them at an earlier time point,” Kelly said. “Perhaps some day we can use these therapies instead of long courses of chemotherapy. We won’t know until we complete all the clinical trials. We offer some of these clinical trials to help us get the information we need to make a standard of care recommendations.”

Other kinds of immunotherapies use medication to stimulate the body’s own T-cells to work better against illnesses such as Hodgkins lymphoma, melanoma and lung cancer, for example. The therapies are being used earlier and earlier in treatment as they have lower risks than radiation and chemotherapy.

“We’re still testing these medications in clinical trials,” Kelly said. “We’re accumulating the knowledge, so hopefully it will change what our current practice is. They are not without side effects.”

Hypothyroidism is one example. However, medication can replace the hormone that the thyroid would naturally generate. Kelly said that rarely, inflammation of the lungs or heart can also occur.

Further research on side effects is ongoing.

“As we learn more about it, we’ll be better able to use which medications in which patients at which doses,” she said.

Other trials are looking at novel vaccine treatments that target cancer cells to treat brain tumors.

Sharing information through enrollment in the National Cancer Institute’s cooperative group has helped doctors succeed in treating childhood cancers.

“What we found is by having enough patients on the same protocol, we can find out what works and what doesn’t,” said Steven Lipshultz, MD, who leads research and treatment on cardiac oncology and is president of UBMD Pediatrics at Jacobs School of Medicine. “We were able to take these rare diseases we were able to get rapid advances and modifications and learn about side effects and toxicity.”

Treating adult cancer has not progressed nearly as much as with pediatric cancer, partly because of age-related comorbidities. Another difference is the quality of life for the expected lifespan. A 75-year-old patient would have another five or so years expected lifespan, unlike a child. The long-term side effects weigh more heavily with younger patients.

That is why developing effective treatments that preserve healthy cells is so important. For example, chemotherapy often damages the heart as a side effect.

“What we don’t want to do is create a generation of cardiac cripples or people with so much disability that they cannot get on with their life,” Lipshultz said.

Lipshultz was involved with developing dexrazoxane hydrochloride, a drug that allows chemotherapy to kill cancer cells while protecting the heart from the chemotherapy. This is part of the strategy of balancing oncologic success while preserving quality of life.

“Even 18 years later, we’ve pulled back these patients who had chemotherapy as children and their hearts are significantly stronger because of this medication,” Lipshultz said.