A Brighter Future: The Evolution of Childhood Cancer Treatment

Saro Armenian, DO, MPH

Around 15,000 children are diagnosed with cancer yearly. Despite being a small proportion of all cancers, childhood cancers are devastating as they impact families during vulnerable periods and result in the loss of decades of life.

Common childhood cancers include acute lymphoblastic leukemia (ALL) and brain tumors. The financial burden of childhood cancer on families is significant, with parents often needing to take time off work or quit their jobs to care for their child. This can have profound impacts on family dynamics and the well-being of other children.

However, the treatment of childhood cancers has undergone significant advancements in recent decades, leading to improved survival rates and reduced long-term effects. These improvements can be attributed to ongoing research, more targeted therapies, and increased supportive care for pediatric patients.

While childhood cancer remains a complex and challenging disease, experts like SaroH. Armenian, DO, MPH, is optimistic about the landscape. Continued research and development are essential to ensure that children with cancer receive the best possible care.

In an interview with Targeted Oncology^TM, Armenian, Barron Hilton Chair in Pediatrics and the director of the Division of Outcomes Research/Intervention in the Department of Population Sciences at City of Hope Cancer Center, discussed the unique challenges facing children diagnosed with cancer and their families and what lies on the horizon.

Targeted Oncology: What is the prevalence of childhood cancers compared with adult cancers?

Armenian: In the US, it's somewhere around 15,000 children will be diagnosed with cancer each year. Despite that alarming number, that's still a small proportion of [patients] with cancer diagnosed in the US, because cancer is primarily a disease of aging. At any given time, in terms of the proportion of cancers, [childhood cancer] makes up less than 5% of all cancers in the US.

What makes childhood cancer so different and so devastating, in addition to the fact that you are compromising an entire family life at a very vulnerable period is the decades of life that is being lost, which is not the same in the decades of productivity and contribution and membership in the society.

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Are there any types of cancers that are more prevalent in children?

Cancer in children can happen in any part of the body, and in fact, there are many, many different subtypes of cancers, but there are some that are more common than others. Acute lymphoblastic leukemia, ALL, is probably the most common type of leukemia that we have that we see in children. And then, surprisingly, brain tumors are actually quite common as well. Some are very difficult to treat for brain tumors, and some not as much. And then after that, you really get into a whole host of cancers that impact various parts of the body, whether it's the hematologic system, the lymph nodes, or specific organs.

Can you discuss the financial burden that childhood cancer can place on a family?

It is actually a very important point. This is a light that has not been shed in previous conversations around childhood cancer. Most of the focus today has really been thinking about getting the child through the cancer treatment whole and cured, so that they live a long, healthy, and productive life. Cure is increasingly achievable for many childhood cancers. And now we are starting to think about, what is the price of cure, what is the roadmap to cure, and can we do a better job?

One of the ways is to think about the acute toxicities associated with the treatment, and can we minimize those? The other way is to think about what we call the financial toxicities associated with childhood cancer treatment. That has substantial impacts on a family dynamic. [For example,] in a family with 2 working parents and several young children,when a child is diagnosed with cancer, oftentimes one of the parents will have to either take time off, quit their job, or essentially try to work from home or use some other flexible strategy that has direct financial consequences to the household. It also has psychosocial impacts, because now you are taking a parent out of a dynamic of the care for the other children, and that level of disruption can have profound impact. That is in just in the context of 2 available parents, Single parents who are navigating this journey have an especially hard time both navigating their own profession, the child's cancer care, as well as the other siblings’ care. So increasingly, people rely on extended family and support, but not everybody lives in large nuclear families anymore, and that becomes an increasing challenge for many of our patients and their families. There is direct data to show that the more severe the financial impacts are during cancer treatment, the worse the outcomes are for these children, because it impacts their ability to get to their treatments on time or get the appropriate prescription medications, [afford the] copays, and all the other aspects that drive the financial costs of care.

What are some of the short- and long-term issues that can emerge when children are diagnosed with cancer?

The reason why we can cure the overwhelming majority of children diagnosed with cancer today is because we have been able to, over the years, intensify the therapies that we can give them that adults would otherwise not be able to handle, in addition to other strategies like being more precise in our treatments. But one of the things we recognize is that delivering intensive chemotherapy to a physically growing child has direct consequences in terms of the toxicities of the treatment, not just in the short term. It has a real impact on the long-term health of the survivor.

We currently have over 500,000 estimated survivors of childhood cancer who were treated at a very young age at a time when their organs were developing. There are real issues that develop in the second, third, and fourth decades of life. Increasingly, we are starting to recognize that there is an accelerated aging look that many of these patients have developed. [They also] develop health conditions that you typically would not see until individuals are in their seventh and eighth decades of life. We are seeing them in our children who are now becoming young adults. Cardiovascular disease, pulmonary disease,endocrine effects, and other late effects that have lifelong physical and economic tolls on these [patients] as they transition into adulthood. For some, [these issues] can impact their independence and their ability to achieve their career goals.

How can physicians and clinicians better support these patients through their journeys? 

When cure is an expected outcome for many of our children with cancer, what is also expected that they are going to live for decades after their cancer treatment. Many of our children get outstanding care during their treatment and through the majority of their childhood. But many of our children being treated in children's cancer hospitals, but typically in their early 20s or so, many of these [patients] have transitioned out into the community, and that period of transition is probably the most difficult to navigate for our childhood cancer survivors. The transition is happening at a time when they are at risk for developing late effects of therapy, and if that transition does not happen appropriately with educational material and direct instructions for screening for these late effects of therapy,[patients] can have major medical issues that develop that are often under recognized in the general community.

There are a few places, like here at City of Hope Children's Cancer Center, where that transition happens all within the umbrella of one hospital or one health system. That allows for the smooth transition from the pediatric setting to the adult setting without compromising the need or the ability to do surveillance and monitoring, and that model is increasingly been recognized as the most optimal way to make the transition happen. We try to activate our survivors so that they have the appropriate tools to demand from their primary care providers.

Are there any policy changes or initiatives that are aiming to help improve outcomes of children with cancer?

Thankfully, in the pediatric oncology community, even though the average cure rates now exceed 85% across cancers, we have never rested on our laurels. There are a number of efforts now that are tackling childhood cancer. We are at a junction where we as a pediatric oncology community are asking ourselves, how can we do better?

We are fully cognizant that the traditional chemotherapy drugs that we have been giving children have toxic late effects. When possible, we have been fully embracing more targeted approaches that focus on the genomics of the tumor or focus on how to harness the immune system of the [patient] to target the cancer rather than broad therapies that are not necessarily specific for the cancer itself. That is being increasingly introduced upfront at the time of diagnosis, and biotherapies and immunotherapies are really at the forefront of where we are going to go as a pediatric oncology community.

We have also started to think about more strategies towards personalization of cancer treatment, understanding the tumor biology, and, when necessary, increasing the intensity of therapy to optimize the cure for high-risk [patients] or deescalating the therapy based on the genomic profile of the tumor or the characteristic of the patient. That personalization is going to continue over the next several decades. That is a paradigm shift that has emerged over the last 10 to 15 years in the survivorship realm as we think about the optimization.

Many of the treatments that were previously done exclusively in the inpatient setting are being transitioned to the outpatient setting because we recognize that most patients prefer to be home and that is the best environment for them. Then, helping [patients and families] navigate a better awareness of the more holistic approach to care has been key. Thinking about supportive care strategies to get patients and their families through, recognizing the unique socioeconomic demands of the associated economic drivers of outcomes. We are much more in tune and aware of interventions to address those needs during those cancer treatments that we were 10 to 15 years ago.

As far as the survivorship realm, the need to have accessibility of medical records and treatment history for [patients] as they transition into adulthood is key. There are number of initiatives across the [National Institutes of Health (NIH)] right now where we are really pushing for interoperable medical records, so that a patient, for example, who had their treatment done in California, but then decided to go to the east coast for college and stay there for their work, still has access to their medical records. That level of communication across medical records and health systems has not happened until now. The NIH and the [National Cancer Institute (NCI)] are invested in making sure that the patient's own their records and can share them as needed with the providers that they are seeing. Before this, they were fully reliant on the primary cancer treatment center for that information, and that was a big disservice.

What are some challenges that still exist in the field?

We are entering an era of understanding individual genomic factors that drive outcomes and response. Genetic biomarkers have helped us rethink our treatment approaches, but they have also introduced a lot of challenges. The more we understand the uniqueness of certain pediatric cancers, it creates this catch-22 where we do not have enough numbers sometimes to be able to develop the appropriate clinical trials that sometimes require hundreds, if not thousands, of patients to be enrolled to be able to answer a specific research question.I think that is where we struggle as a pediatric oncology community. To overcome this, we have been increasingly reaching out, not just to our international colleagues for more collaborative work, but also to our adult colleagues to try to find areas of overlap where we can learn from each other in certain cancers. The classic one is Hodgkin lymphoma, and now we recently completed a seminal intergroup study between the Children's Oncology Group as well as the adult cooperative groups where [adult and pediatric patients] with Hodgkin lymphoma were treated on one protocol. We recognize that there are shared biologic pathways that we can focus on. The reason that that study came about is because it was informed by both pediatric patient studies as well as adults. I think that level of collaboration and cooperation is probably going to happen moving forward, and that gives me a lot of optimism.