Brain and spinal cord tumors are the second most common cancers in children, accounting for 1 out of 4 childhood cancers. Despite intensive treatment, children with histologically diagnosed high-risk medulloblastoma, supratentorial primitive neuroectodermal tumor of the central nervous system (CNS-PNET), and pineoblastoma (PBL) continue to have suboptimal outcomes. James M. Olson, MD, PhD, Professor of Pediatric Hematology/Oncology at University of Washington School of Medicine, and colleagues found that molecular profiling of patients with CNS-PNET/PBL revealed a significant proportion of patients were initially misdiagnosed and consequently overtreated and that other patients have a better prognosis than previously realized. i3 Health spoke with Dr. Olson about these findings and their implications for pediatric brain tumor practice.
What would you say are the key takeaways from the results of the ACNS0332 Trial?
James M. Olson, MD, PhD: The key take-home message of our recent paper is that using a microscope to make the diagnosis for some types of pediatric cancers will lead to incorrect diagnosis in some cases, and over or undertreatment of the child may be associated with that.
Can you speak more about the importance of molecular profiling at initial diagnosis?
Dr. Olson: In our study, 71% of cases of a certain type of tumor were diagnosed as a central nervous system PNET when they were actually glioblastoma or other forms of cancer. In those cases, the kids received more therapy than was helpful to them, and that caused side effects that could have been prevented if they had been diagnosed properly at the time. The molecular studies that are available today would prevent all of that if the child was diagnosed with genomic studies up front.
We can't fault my colleagues and our team for what happened in the past because these techniques were not available at that time. This is a new technique that is available for diagnosis for the first time this year, so I want to be careful not to convey that these children were misdiagnosed. We now have a new tool that will help us diagnose them properly and help them get the right treatment for their type of cancer.
What would you say are some of the most challenging aspects of managing pediatric brain tumors?
Dr. Olson: The most challenging aspects, of course, are that you have a child who is in a life-and-death situation; you're meeting the family and have to earn their trust to help them navigate a path that they never expected to be part of their lives. We also allow ourselves to fall in love with every one of these kids and, if they die or if their tumor progresses, that's a big emotional hit.
That's the emotional side of what is most difficult. On the other side of it, sometimes we know what is best for these children and we have to fight with insurance companies to get approval to do the right thing. This is a good example of that. We know now, with no uncertainty, that the proper way to diagnose these kids is to do molecular studies at the time they are diagnosed, and yet, more often than not, the request for insurance funds for these molecular studies is initially turned down. We have to spend a lot of time and energy fighting to get the approval to do the right studies for these kids.
What are some best practices that you would recommend to community oncologists who are managing pediatric brain tumors?
Dr. Olson: Because pediatric brain tumors are so rare, community oncologists should refer these patients to an academic center that has a strong pediatric brain tumor program. There are a lot of types of cancer that are best treated in the community, but, at least for initiating therapy, these kids should come to a very well-resourced pediatric brain tumor clinic. Then, those of us in those types of clinics should try to get the kids back into their community for ongoing care as quickly as we can.
Whether you're in an academic setting or in a community setting, it's really important to get the diagnosis right. We really need to do molecular testing at the time of diagnosis rather than at the time of relapse, which is how it's often done now. By then, we've missed an opportunity because it's so much harder to cure cancer after relapse than at the time it's diagnosed.
What are some promising advances in pediatric brain tumor treatments that you expect to see in the near future?
Dr. Olson: One major advance that has come through in the past few years is that there are now drugs that target a specific pathway, so we have some kids who have better chances of survival just by taking a pill a day that has almost no side effects than if we treated that same child with radiation and chemotherapy and did the traditional approaches. So there are treatment options that we can use if we do proper genomic studies and learn what is driving the pediatric cancers.
Also, I am hopeful that we'll see immunotherapy opportunities where we can educate the patient's own immune system to go after and kill the cancer cells. The first clinical trial with this concept opened at Seattle Children's Hospital recently, and I'm hoping that there will be a lot more of that research and progress in the future.
Is there anything else that you would like to add for community oncologists?
Dr. Olson: For children with cancer, there's an average of a nine-month lag from the time that the first symptoms present and the time that the child is actually diagnosed with cancer. The problem is that many signs and symptoms of pediatric cancer are also signs and symptoms of very common childhood illnesses.
It's really important to have on your radar: Did the headaches stop after a week or two? Did the symptoms stop in the timeframe that you would expect if it was a common pediatric illness? If they're the same or progressing, it's reasonable to do a deeper workup and to rule out things like brain tumors or other types of cancer.
About Dr. Olson
James M. Olson, MD, PhD is Member at the Fred Hutchinson Cancer Research Center, a Professor of Pediatric Hematology/Oncology at University of Washington School of Medicine, and an Attending Physician at Seattle Children's Hospital. His primary research interest is focused on discovering new therapies for children with brain cancer.
For More Information
Hwang EI, Kool M, Burger PC, et al (2018). Extensive molecular and clinical heterogeneity in patients with histologically diagnosed CNS-PNET treated as a single entity: a report from the Children's Oncology Group randomized ACNS0332 trial. J Clin Oncol. [Epub ahead of print] DOI:10.1200/jco.2017.76.4720
Transcript edited for clarity.