The treatment and support that children with cancer receive has advanced over the past 20 years, but more progress to improve the cure rate is on the horizon.
In 2003, Megan Piotrowicz was a typical 12-year-old girl, an age when aesthetics become more important and hobbies like playing basketball consume more after-school time. She was one of five children in an incredibly supportive family.
Then she was diagnosed with Ewing sarcoma in her skull. This was a rare place for this bone cancer to occur, as it often appears in patient’s legs and arms.
Piotrowicz was treated at Children’s Hospital of Philadelphia, an institution her family considers a “jewel that lies in our backyard.”
She was enrolled in a clinical trial that compared a two-week and three-week rest period between chemotherapy treatments. She was assigned the shortened amount of rest period between the three rounds of chemo she received.
“I look back at my time as a patient and I truthfully consider myself lucky,” Piotrowicz says. “I didn’t get sick. I didn’t have those throw-up bouts at home, anything like that. I think I just got sick on my first treatment, and then I was good.”
Her tumor shrank from the size of a tennis ball to the size of a golf ball in three months, then she underwent a tumor resection surgery to remove it.
The surgery went so well, according to her neurosurgeon, that he reconstructed her skull at the same time, which would typically occur during a separate surgery.
After the eight-hour surgery, she was in the intensive care unit overnight and was home the next day to celebrate her mom’s and aunt’s birthdays. She was deemed cancer free on December 13, 2003.
Piotrowicz is grateful that she and her family opted to participate in a trial that provided evidence to further the pediatric oncology space, especially because she had a great outcome from her treatment.
Looking back 20 years, one of the biggest changes made in the pedi- atric cancer space was the National Cancer Institute’s merger of four clinical trial groups into one.
“That was a huge transformation. Since that merger, all of the pediatric oncology experts in the country have worked together,” says Dr. Alan S. Wayne, chief of the division of hematology-oncology, director of the Cancer and Blood Disease Institute and the Alfred E. Mann Family Foundation Chair in Cancer Research at Children’s Hospital Los Angeles.
“We were brought into one large cooperative group in North America so we could become even more integrated, systematic, organized and coordinated in our approach to developing and studying new therapies for children with cancer.”
This led to research focused on the arsenal of therapies available to oncologists, including drugs, but also radiation, surgery, supportive care and chemotherapy, and assessing how best to combine them in newer and safer ways.
Better coordination leads to better scientific design of the trial, and more collaboration leads to larger and more informative trials that reach accrual and final analysis more quickly — both critical elements in advancing care.
That’s not to say there was no collaboration in pediatric oncology research before this time. In fact, the community of pediatric oncologists have always worked together through cooperative groups like the Children’s Oncology Group, experts say.
“The National Cancer Institute basically provides an infrastructure grant to fund 220-plus centers across North America so that if you are a child with newly diagnosed leukemia and you walk into any pediatric cancer center, you will probably be offered the same clinical trial, whether you’re in Houston, Seattle or Los Angeles,” adds Dr. Susan Blaney, director of Texas Children’s Cancer and Hematology Center.
Researchers have also learned more about the molecular genetics of cancer specifically in children, which has allowed physicians to risk-stratify patients and determine which patients are better suited for certain treatments.
“Those things we can do today with sequencing are almost unfathomable compared to what we could do 20 years ago,” says Dr. Stephen P. Hunger, chief of the division of oncology, director of the Center for Childhood Cancer Research and the Jeffrey E. Perelman Distinguished Chair in the Department of Pediatrics at Children’s Hospital of Philadelphia.
“That’s improved our understanding of cancer. It’s identified potential therapeutic targets but it’s also been incorporated into routine patient care so you’re better able to pick out who are the patients at highest risks and how do we treat them differently? And conversely, who are the patients with extremely good risk that we ought to see how maybe we could either dial things back a bit or at least not further intensify therapy?”
This has also opened the doors to the use of precision medicine and cellular immunotherapy in these patients, including the use of CAR T-cell therapy in children.
Wayne was the clinical director of pediatric oncology at the National Cancer Institute in 2013 when he helped lead the development of a collaborative study to assess the use of CAR T-cell therapy in children with highly resistant acute lymphoblastic leukemia, the most common childhood cancer.
Results from this phase 1 trial of CD-19-targeted CAR T cells were published in The Lancet in 2014. Of the 20 children with leukemia in the study, 14 went into remission with a single dose of the cells. Research like this led to the 2017 U.S. Food and Drug Administration’s approval of Kymriah (tisagenlecleucel), the first commercially approved gene therapy.
CAR T-cell therapy has also been used for other blood cancers, says Dr. Will Parsons, deputy director of Texas Children’s Cancer and Hematology Center, who specializes in precision medicine research.
“There’s cases where I think one of the first patients treated (with CAR T-cell therapy) about 10 years ago now, and they’re still doing quite well today,” he adds. “And that’s a patient whose cancer had received every possible treatment they could get. We would normally expect the life expectancy to be weeks, months ... so really amazing progress in precision oncology and immunotherapy.”
Assessing the genetics of each patient and their tumor has also been helpful in potentially preventing the overtreatment of children. Precision oncology allows cancer teams to aid in decision-making to identify the optimal treatments and avoid unnecessary toxic ones to potentially improve a patient’s outcomes.
An example of this being utilized is for medulloblastoma, a common malignant brain tumor in children. Previously, children with medulloblastoma — a cancer that occurs in the back of the brain and the cerebellum — would undergo surgery to remove as much of the affected area as possible, then chemotherapy and/or radiation depending on how well the surgery went.
Now physicians focus on reducing the toxic effects of those treatments based on results from pathology, including genomic analysis.
That’s what Eugenia Chong’s daughter, Florence, underwent when she received a diagnosis and was treated for stage 4 medulloblastoma in the summer of 2020 when she was 23 months old. Florence was throwing up in the morning and would crawl instead of walk, which Eugenia, who is a nurse, thought was associated with changes in everyday life from the COVID-19 pandemic.
As the symptoms persisted, Eugenia took Florence to her pediatrician and other specialists and eventually to the emergency department at Children’s Hospital Los Angeles, where a CT scan showed that Florence had a very large tumor.
This began her 40-day hospital stay, which included inserting a drain into the ventricle of Florence’s brain to offload some of the fluid that caused her symptoms. Florence then underwent surgery to remove the mass and pathology reports determined her diagnosis, after which chemotherapy was started.
“(The hospital stay) was obviously very, very scary. It was frightening,” Eugenia recalls. “I was also four months pregnant at the time with my son. ... It was challenging that only one parent was allowed at a time to stay with her.”
Despite the COVID-19 restrictions at the hospital, Eugenia tried to make light of the difficult situation with her husband, Rich.
“(We) had a conversation where we said, if our child was to be neutropenic and not have a defense, this actually might be the best time where people are distancing, washing their hands and wearing masks,” she said. “So I would say there was a silver lining.”
Not only have advancements been made in the treatment of children with cancer, but also in the support that children, their parents and care- givers receive throughout the cancer journey. This includes the care needed for children as they receive toxic therapies. This, in turn, may improve survival rates for children, experts say.
During her hospital stay, Florence was visited by child-life specialists who provided services to distract her from painful procedures and engaged her to communicate her needs and fears at an age- appropriate level.
“They provided a type of presence that was nonclinical, which actually created a less scary environment for a child,” Eugenia says. “They also provided support for me, giving me breaks so that I could just leave the room for a little bit.”
In addition, there is more supportive care for patients as they enter the survivorship phase.
“We didn’t used to have a science really called survivorship because we didn’t have enough survivors,” Blaney says. “But it’s very important.”
As survival rates have improved from 20% to 80% over the past few decades, cancer teams have learned more about survivorship and the short- and long-term side effects of treatment, including effects to the brain, heart, lungs and fertility.
Piotrowicz froze her eggs as an adult because the treatment she had undergone increased her risk for early menopause.
“My doctors made sure that (they asked), ‘Do you want a family? Is that important to you? This is what you need to think about,’” she recalls. “They asked me when I was 18, and my mom was like, ‘Let’s get her through college.’ It’s not something that my mom or my dad (were) thinking about.”
Services such as Passport for Care, which was developed with the Children’s Oncology Group, are available at all pediatric institutions and allow childhood cancer survivors and their physicians to access information about treatment the patient underwent when they were too young to remember the technical names of treatments. It also provides patients with updated guidelines on what monitoring to undergo based on the treatment they received when they were younger.
Although significant advancements have been made in how children with cancer are treated, there are unmet needs that persist.
“We are not far enough along; we’ve got so much more to do,” Wayne says. “I feel like we’re just scratching the surface despite all the progress.”
Wayne added that more focus is needed to make therapies safer, more effective, less demanding and less expensive.
In addition, more money is needed to dedicate to pediatric cancer research, a cause that Piotrowicz has been involved with over the past six years at the institution where she received her cancer care.
Now aged 31, she is starting a new role at Children’s Hospital of Philadelphia as a major gift officer for the neuroscience center.
“I take (this) very seriously,” she said. “I think that’s the best part of my job — making (contributors) feel really good. There’s no way to pay these doctors back, so this is their way of doing it and making them feel good about it is something that I feel is really special.”
Making cancer treatment less expensive and more accessible may also impact the disparity that persists. Although many big cities have centers of excellence for pediatric cancer, the travel alone can be a burden on a family. This burden may also persist for people who live in the same city as these centers.
“The kids in inner-city Northeast Philadelphia, which is five to seven miles from here — that can be a world of difference,” Hunger says. “It’s not so much the distance; it’s the barriers of knowledge, access, dealing with the struggles of life. If you’re from a family that is worrying about how to put food on the table, it’s a little hard to manage the intricacies of tertiary care of pediatric cancer, although we work very hard to support them.”
As researchers and physicians continue to push the area of pediatric cancer forward, they often look back on the past 20 years and how much progress has been made.
“Every time we see one of these new therapies help a child, it truly is miraculous,” Wayne says. “And to see a child discharged, go home to play and return to school, needless to say, it’s what we live and work for.”
Both Piotrowicz and Florence have been cancer free since they underwent treatment, which is a testament to the advancements that have been made over the last two decades.
“(Florence) started preschool,” Eugenia says. “I just got her preschool photos back, so she’s made friends and she’s gained a lot of independence. Her words have exploded and her personality has really developed. She’s just wonderful. You would not be able to know that she’s gone through cancer treatment.
To learn more about how Eugenia navigated Florence's cancer diagnosis in the midst of the COVID-19 pandemic, listen to this "Cancer Horizons" podcast episode.
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