Sammy Loch began experiencing debilitating headaches in 2009. She was a sophomore in high school at the time. When she went to see her primary care provider, they diagnosed her with migraines and prescribed medication to help dull the pain. When her migraines persisted, her doctor recommended Loch get an MRI to rule out anything more insidious.
Days before the MRI, Loch got dressed in a beautiful purple gown, her curly hair bounding in tight curls just at her shoulders. She had been looking forward to the homecoming dance for weeks. She was all smiles, but the throbbing pain in her head was still there. She powered through the dance, determined to have fun. She was completely unaware her world would soon be turned upside down as she danced in the high school gym surrounded by her friends.
On Tuesday, Oct 27, 2009, Loch went in for an MRI.
“The technician was so bubbly and nice,” Loch said. “She told me about the elaborate costume she was working on because Halloween was only a few days away. I remember everything about her demeanor changed when she came back in the room after my scan. My heart sank. I knew something was seriously wrong.”
That night around 8 p.m., her family got a call. Her mother answered, repeating aloud what the voice on the other end of the line was saying. “There’s a mass. You need to go to Seattle Children’s as soon as possible.”
Everything seemed to stop as those words hung heavy in the air.
“It’s cancer,” Loch said. “I just knew it.”
Loch went to her room while her mother and brother stood frozen in place. She packed a hospital bag, printed out directions to the hospital and tried to process the unimaginable.
She was diagnosed with medulloblastoma on October 29. That day, her treatment started – a grueling journey that would include surgery, radiation, chemotherapy and countless months spent at Seattle Children’s, her new home away from home.
Beating the odds
Brain tumors are the leading cause of disease-related death in children, and medulloblastoma is the most common malignant embryonal brain tumor. About 400 children are diagnosed each year with medulloblastoma in the U.S.
Nearly 20 years ago, a pilot study was conducted by the Children’s Oncology Group (COG). The study (99701) aimed to determine if carboplatin, a chemotherapy drug used to treat a variety of cancers, in conjunction with radiation and chemotherapy, could be given safely in children with high-risk medulloblastoma. During that initial study, it wasn’t clear whether the addition of carboplatin would help all children with medulloblastoma, or a subset of children with the disease. Medulloblastoma is a rare cancer, but there are various subgroups of the disease. What Dr. James Olson, an oncologist at Seattle Children’s, professor at the Fred Hutchinson Cancer Research Center (FHCRC) and the University of Washington School of Medicine, was hoping to determine was whether a specific group of children with medulloblastoma would benefit more than others with the additional treatment of carboplatin.
Olson, having an interest in improving survival rates for children with brain tumors, embarked on a mission to take that pilot study and go one step further. He decided to lead a clinical trial aimed at helping to improve treatment options and survival rates for children with high-risk medulloblastoma and COG offered that opportunity through its trial ACNS0332, which was carried out at its over 200 member institutions.
Today, the results from the trial published in JAMA Oncology, and they are being called monumental.
The COG study ACNS0332, which was funded by the National Cancer Institute, found that therapy intensification with carboplatin improved survival significantly. The increase wasn’t marginal, it was the largest Olson has even seen, in any trial – 19% for children with high-risk Group 3 medulloblastoma. The addition of carboplatin during radiation improved survival from 54% to 73% for children in that group.
“Since the advent of radiation and chemotherapy over a half century ago, we’ve never seen this big of an improvement in one clinical trial for kids with brain tumors, to my knowledge,” said Olson. “From this point forward, for kids with the Group 3 subset of medulloblastoma, what this means is 20 more children out of every 100 will survive the disease than would have survived in the past. It’s a forever improvement, and it gives us a clear roadmap for the future.”
Dr. Sarah Leary, medical director of the Pediatric Brain Tumor Program and the medical director of clinical research in the Cancer and Blood Disorders Center at Seattle Children’s Hospital, says the results are a leap in research, not simply a step forward. She joined Olson mid-way through the trial and helped analyze the data.
“This trial saved lives,” Leary said. “Biologically, there are different groups of medulloblastoma, and increased therapy is helpful to one particular group. That kind of difference, saving one out of five kids, is monumental. It also shows how important it is to make sure you’re diagnosing the group right from the get-go. Not only will the results from this trial save lives in the future, but some of the kids who were part of the study are alive today because they had access to the study.”
Although both researchers agree that the ultimate goal is to replace the need for radiation and chemotherapy, this study helps move research forward and give hope to families impacted by this debilitating disease.
One of the many salient points is that not all children with medulloblastoma will benefit from the addition of carboplatin, but for those who have a specific subtype, they do see a significant improvement in survival.
From this clinical trial, three things are clear:
- Molecular diagnosis is critical to improving outcomes and better understanding a person’s unique disease.
- Aggressive treatment based on molecular diagnosis improves brain tumor survival for a group of high-risk children with medulloblastoma.
- Clinical trials can save lives and collaboration between institutions, nationally and internationally, is imperative.
“We could tell we were on the cusp of a genetic revolution,” Olson said.
A passion for pediatrics
There are thousands of moments throughout a person’s life that have the potential to dramatically alter an individual’s path or journey. For Olson, one of those profound moments happened as a budding doctor.
While in medical school, he found himself continually gravitating toward the oncology units while on rotations. He would spend hours at the bedsides of patients, often until late into the evening offering reassuring words and a calming presence. He saw firsthand the tragic and insidious toll cancer took on people.
As a PhD student, he studied ways to image the brain. He worked extensively with cancer patients and conducted research studies he hoped would help unravel the mysteries of the brain. Participants in his research studies knew Olson’s research wasn’t going to save their lives, but it would help people in the future.
“I will always be incredibly grateful to them,” Olson said. “They chose to spend time they knew they wouldn’t get back helping others who would benefit from the research.”
From that work, he felt a deep-seated commitment to individuals with brain cancer.
Finding a specialty
Olson never planned to specialize in pediatrics, but that changed one day when he heard devastating news. A little girl he was helping to care for passed away from a neurological disease. That was the first time he witnessed the death of a child who was in his care. There was nothing he, nor any other care providers, could have done, but the loss weighed heavy on his heart.
After the child passed away, her parents scoured the halls of the hospital looking for Olson. Even in the face of so much tragedy, they felt compelled to tell him something. Before they left the hospital one last time, they wanted to say thank you. They said because of the kind words Olson had shared with them, they believed their child’s death was as beautiful as her birth. They told Olson he had a rare talent and that he had left them with a gift: hope.
That day, Olson tore up his applications to the other specialty he was planning to train in. He decided not just to help children beat the odds, he wanted to change the odds altogether. Back then, survival rates for pediatric cancers were far too low, and so the cornerstone for which he rooted his care and research revolved around a mission – to help children and their families thrive.
“I realized there was more to medicine than curing people,” Olson said. “It’s about walking a journey with families, no matter what the outcome will be.”
And so, his journey began – a path he had not intended to take, but one that would change outcomes for children battling cancer.
The study was conducted from 2007 to 2018 with nearly 300 children participating in the trial. Participants ranged in ages from 3 to 21. More than 200 institutions from around the world were involved. It’s the largest international trial involving children with high-risk medulloblastoma ever conducted. Olson was the lead investigator and Leary was the co-investigator.
Although medulloblastoma is a broad term for the type of cancer, genetically, medulloblastoma is now considered four different diseases based on molecular grouping. This trial analyzed participant results based on the genetic analysis of their cancer.
“Genetic analysis is essential,” Olson said. “It not only helps us decide the right treatment, but it helps us make the right diagnosis from the beginning. It helps us decide the right treatment to give to the patients who will benefit the most and avoid toxic treatment to those who won’t benefit at all. Tumors may look the same under a microscope, but if they are genetically different, they will respond differently to various types of treatment approaches.”
Olson says genetic analysis helps determine better treatment plans and provide correct diagnoses. He says the early pilot study provided incredible insights into the benefits of molecular diagnosis. He said they learned that for some types of pediatric brain tumors, the pathologic diagnosis was incorrect 70% of the time. That potentially means that 70% of the time, the best and most effective treatment approach may not have been utilized. It’s one of the reasons Seattle Children’s is spearheading integrated molecular diagnosis.
Historically, Olson says there were two types of clinical scientists in oncology – lumpers and splitters. Lumpers were those who lumped all those together who had tumors that looked similar under a microscope. Lumpers believed an already rare cancer should be treated the same, rather than splitting the group apart. That’s what splitters do – split the group. Today, Olson says genomics has become an important part of what we do, and because of that splitters are winning. When we split individuals by genetic diagnosis, small clinical trials can be directed specifically toward that very specific cancer.
“Essentially, we’re making an already rare cancer even rarer,” said Leary. “It’s important to give the right therapy to the right child,” Leary said. “This trial emphasizes why molecular diagnosis is needed – so we can provide the best treatment and diagnose children appropriately from the beginning.”
A foot in two worlds
Leary says the study results are exciting, but there will always be questions that keep her up at night.
“I have a foot in both the research world and a foot in the clinical side,” Leary said. “I’m constantly asking myself, ‘How do we do better?’”
Leary says Seattle Children’s is at the forefront of molecular and genomic analysis. Many centers across the country don’t have the capability. At Seattle Children’s, researchers and oncologists are working to create an international standard, and the capacity to use molecular diagnosis is game-changing.
“I spend a lot of my time asking myself if each of our kids is getting the best for them and their family,” she said. “When I look at a child, I wonder if they are getting the best therapy. There are no good tumors. They are all bad. What’s most important is getting the right information and using that information to make the best treatment plan for that unique child. Sometimes, research is the only way to answer that question.”
The future of precision medicine and cancer research
For Leary and others at Seattle Children’s, precision medicine is the future. Through collaboration, they are trying to better understand what’s best for each individual patient and their family. To do that, they need more data.
That’s why collaboration and philanthropic support are key, and also why researchers and oncologists at Seattle Children’s are spearheading and leading many consortiums worldwide to further advance pediatric cancer research. Only about 4% of government funding is allocated toward pediatric cancer research. Philanthropic support by private donors are instrumental in helping to advance pediatric cancer research, find better, safer treatments, and help more children in need.
This trial was done in part by institutions worldwide, led by researchers and oncologists with a similar mission – to find better treatment options for children with medulloblastoma.
Seattle Children’s is internationally known for developing better ways to care for young people with cancers or blood disorders. Many Seattle Children’s oncologists are leaders in research to help transform treatment and improve outcomes.
“We have a long journey ahead, but we’ve made enormous progress,” Olson said. “We’ve improved survival for this group of kids to 73%. There is still too much toxicity, but we’re currently working on additional therapies that could replace radiation and chemotherapy. That’s our next step.”
Olson says his research is fueled by the incredible support of his patients, and the generosity of the community to fund this lifesaving work.
“The rich scientific environment where science and medicine are intertwined, it’s embedded in the DNA of Seattle Children’s,” Olson said. “Our outcomes are far higher than the national average because of that intersection, and because of the dedication of our staff to identify problems and develop solutions.”
Children with cancer and blood disorders come to Seattle Children’s from all over the world to take part in research studies of new experimental treatment options that are available only through clinical trials. The children and young adults Seattle Children’s treats also have access to clinical trials like ACNS0332 offered through the Children’s Oncology Group (COG), the world’s largest organization devoted exclusively to childhood and adolescent cancer research which has nearly 100 clinical trials open at any given time. Seattle Children’s has more open trials than 98% of pediatric academic medical centers. This means Seattle Children’s care team has the widest possible range of trials to consider when recommending options for children.
Year after year, Seattle Children’s is among the five childhood cancer centers in the nation with the most patients enrolled in clinical trials. Through their leadership in the COG, experts at Seattle Children’s help set the global agenda for pediatric cancer research.
“Part of the reason we’ve made such enormous strides in pediatric oncology is because we partner, not only nationally but worldwide, and that’s the key to our success,” Olson said.
Olson and Leary believe the future of cancer research is bright.
“Together, we’re going to cure cancer,” they said.
Seattle Children’s only treats about 10 children a year with medulloblastoma. There is no way this large of a clinical trial could have been conducted at Seattle Children’s alone, but having the resources of research organizations like COG with which to partner makes advances in the treatment of childhood and adolescent cancers possible.
“It would have taken us 100 years to conduct a trial of this size at our institution,” Leary said. “Our collaboration with others is vital.”
“This trial saved our child”
“Children and families provide an enormous contribution when they volunteer to participate in clinical trials,” Olson said. “They are the reasons why we’ve improved survival from less than 25% to 80% over the course of one lifetime.”
And having access to research can save lives.
Leary remembers vividly talking to one mother whose child was enrolled in the medulloblastoma clinical trial. They believe their child is alive because of the carboplatin. She knows without a doubt her child is alive today because of research.
The hope now is to save more lives and to advance treatments even further, so no child has to undergo toxic radiation and chemotherapy to cure their cancer.
“I am constantly thinking about the next trial,” Leary said. “What question can we answer to help more kids survive? Cure is the goal. We won’t stop until there is a cure.”
Today, Loch is doing incredibly well. She’s been cancer-free for more than 11 years.
“Cancer is part of my story,” said Loch. “I am the person I am today because of it. It’s a big part of my identity. In the last 11 years, as I’ve gotten farther away from it, it’s not as central. Over time, it’s become more integrated as a piece of me.”
Loch said cancer taught her about herself and helped her find her way.
“Before my diagnosis I was stumbling through life trying to make everybody else happy. I tried to live up to what I thought other people’s expectations were for me however unfounded they were. Although it seemed like I had it all together, what everyone was seeing was a very carefully crafted mask. Cancer stripped that mask away,” she said.
She said one of the things she always appreciated about Leary was how she included her in every decision throughout her treatment. When asked if she wanted to enroll in the clinical trial, she talked it through with her parents. Ultimately, the decision was hers to make.
“Participating in research was my way to give back and pay it forward,” said Loch. “It’s really exciting to know more people will survive because of the research I was involved in.”
Today, Loch is 27 years old and continues to pay it forward. She is a therapist for people with chronic health conditions, and she regularly participates in fundraising opportunities for pediatric cancer research.
To families currently undergoing cancer treatment, she offers hope.
“While cancer treatment was a horrible experience to have, it completely changed my life for the better. Losing my mask and keeping my positive attitude helped me become who I truly want to be. Half-way through treatment I wrote a poem about cancer called Give and Take. It ends, ‘cancer left me weak but gave me the Strength to find the Courage I didn’t know I had.’ The courage to be myself,” said Loch.
About The Children’s Oncology Group (COG)
COG (childrensoncologygroup.org), a member of the NCI National Clinical Trials Network (NCTN), is the world’s largest organization devoted exclusively to childhood and adolescent cancer research. COG unites over 10,000 experts in childhood cancer at more than 200 leading children’s hospitals, universities, and cancer centers across North America, Australia, and New Zealand in the fight against childhood cancer. Today, more than 90% of the 16,000 children and adolescents diagnosed with cancer each year in the United States are cared for at COG member institutions. Research performed by COG institutions over the past 50 years has transformed childhood cancer from a virtually incurable disease to one with a combined 5-year survival rate of 80%. COG’s mission is to improve the cure rate and outcomes for all children with cancer.