A “very simple idea” could bring new hope to pediatric cancer patients whose cancers return after completing standard treatment, researchers at Florida International University and Miami’s Nicklaus Children’s Hospital say.
Doctors extract cancer cells from “relapsed refractory” Nicklaus patients and send them to an FIU laboratory, where their DNA is sequenced and cells are exposed to dozens of combinations of drugs to see which may be most effective and least toxic. The result is a treatment plan tailor-made for each patient.
It’s all done ex vivo, or outside the body, sparing the patient from side effects and ineffective treatment. “This really will help us provide safer treatment options for patients,” says Diana Azzam, scientific director at the Center for Advancing Personalized Cancer Treatments at FIU’s Robert Stempel College of Public Health & Social Work.
The idea has been around for years, Azzam says. But technological advances have expanded opportunities to apply it. For example, acoustic dispensers now can infuse cancer cells with nanoliters of drugs, meaning smaller tissue samples are needed.
Doctors can use fine-needle biopsies to obtain those samples, rather than requiring surgeries. And once in the lab, researchers can grow the cells in ways that more closely mirror cell growth inside the body.
And it’s relatively fast — taking roughly 10 days to go from drawing cell tissue from solid tumors to having the data showing which drug combination looks best. “Getting samples directly from the patient and adding drugs and identifying what works will get rid of the trial and error that doctors sometimes have to do” with relapsed pediatric patients, Azzam says.
An initial clinical trial involved patients who had exhausted the standard of care in previous treatment. Initially, 21 patients who enrolled in the study had their cells exposed to drug sensitivity. For a variety of reasons, six of those patients ultimately received treatment based on the results. Five of those six, 83%, “demonstrated a significant increase in progression-free survival and objective response rate,” says a study published in the April issue of the peer-reviewed medical journal Nature Medicine.
The trial was funded by a grant from the Miami-based Live Like Bella Childhood Cancer Foundation, created in 2013 by the family of Bella Rodriguez-Torres, who died of cancer at age 10.
“Bella was one of our patients,” says pediatric oncologist Maggie Fader, the trial’s clinical lead and director of Nicklaus’ Sarcoma & Solid Tumors Program.
Pediatrics traditionally gets the lowest amount of research funding, Fader says, and that makes advances in treatment difficult to achieve. The findings from the Live Like Bella grant helped the research team secure a five-year grant from the National Institutes of Health Institute on Minority Health and Health Disparities to see if the success can be duplicated in a larger pool, and to see whether there are different responses among Black or Hispanic patients.
South Florida’s demographics and Nicklaus Hospital’s patient base make it a natural place to measure effectiveness in different minority groups. In addition, roughly three-quarters of Nicklaus patients are on Medicaid, meaning they lack the resources to travel to out-of-state cancer centers where many significant trials are based, Fader says.
This trial also is unusual because it brings the clinical and laboratory arms of medicine together, Fader says. “It’s literally from patient to lab to patient. It’s true translational medicine. It’s true collaboration. It’s working really well.”
While testing continues on more patients, Azzam also is focused on getting her lab certified under federal Clinical Laboratory Improvement Amendments (CLIA), a seal of approval that the data it generates is reliable. CLIA certification is a giant step toward obtaining FDA approval for the treatment program, she says, and that is a big deal for patients because insurers won’t cover treatment without it.
Similar studies have focused on correlation, Azzam says. Her trial is different in that it seeks prospective data to guide a patient’s treatment. They can test hundreds of FDA-approved drugs on living cancer cells in the lab quickly enough to change the course of treatment.
It is important to give patients and their families options, Fader says. “It’s important that when families come in, we’re not just throwing different chemotherapy regimens at them. It’s very hard to look at someone and say, ‘Let’s go ahead with this. There’s a 5% chance that it might help.’”
At the same time, these are patients whose prognoses are “very poor, and we’re not guaranteeing that we’ll find something that will work … Right now we’re looking to see if this gives people more time, more quality.
“There are plenty of diseases that, from the get-go, you sit across the table and tell a family you’re going to do this really hard treatment, and you’re going to have surgeries and maybe radiation, and you’re going to have lots of chemo with lots of side effects. And with that there’s a 20% chance that your child will be alive in five years,” Fader says.
“That is a really terrible sit-down. In the future, if you could say we could do better, that would be really great.”