Childhood Cancer Awareness Month Shines a Light on Treatment Interventions and Advancements

Saro H. Armenian, DO, MPH

Although childhood cancer survivors often experience early-onset conditions, such as secondary cancers, cardiovascular disease, and metabolic issues, interventions and ongoing efforts within the pediatric cancer field are aimed at mitigating these risks. The month of September is Childhood Cancer Awareness Month, which shines a light on these ongoing efforts and calls to action additional research and awareness surrounding this patient group.

“Early detection, early screening, and risk-based management has been the cornerstone of what we do,” Saro H. Armenian, DO, MPH, explained in an interview with OncLive^®. “It’s only recently that we have now taken this one step further to think about prevention strategies that use drugs or therapies because we know who’s at risk based on the treatment they received as a child. We now have a window of time where we can act; not just screen, but intervene to prevent a disease from happening.”

Armenian serves as the Barron Hilton Chair of Pediatrics, as well as a chair and professor in the Department of Pediatrics, director and professor in the Division of Outcomes Research/Intervention, Department of Population Sciences, and the director for the Center for Survivorship and Outcomes at the Hematologic Malignancies Research Institute, located at City of Hope in Duarte, California. He also holds the positions of co-leader of the Cancer Control and Population Sciences Program and director of the Childhood, Adolescent and Young Adult Survivorship Program, also located at City of Hope.

In the interview, he discussed the topic of childhood-related cancers, expanding on the specific long-term health challenges that are present within this patient population. He also explainedwhat interventions are presently available to help mitigate these challenges and highlighted ongoing research within this field.

OncLive: What long-term health challenges are associated with accelerated aging in childhood cancer survivors?

Armenian: Research over the past 2 to 3 decades has brought to light that the successes we have in curing children with cancer come with a price as children become adults. Study after study has shown that children who are treated with intensive chemotherapy, radiation, surgery, immunotherapy, stem cell transplant, [or other therapies] face challenges in their 20s, 30s, and 40s that in a lot of ways mirror what you would expect for individuals in the general population, except those who are in their 60s, 70s, and 80s. These are complications and challenges, such as a different type of cancer. Cancer is a problem of aging. Therefore, these childhood cancer survivors, as they become adults, have a much higher risk of developing another form of cancer, typically occurring at a much earlier age than what you would expect for the general population.

Other aging-related conditions that [have a] much higher [prevalence] in survivors of childhood cancer include cardiovascular disease and metabolic health issues, such as diabetes, hypertension, blood cholesterol issues, and bone health issues. The realization that there are aging-related conditions that are developing in survivors at a much earlier time point is what brought to light this concept of accelerated aging. A lot of our work now is diving into untangling the intersection between healthy aging vs unhealthy aging.

What interventions are being explored to mitigate or reverse these effects in survivors?

Until now, most of the interventions we’ve done to mitigate these issues are essentially offshoots of what we would do for the general population, but we do them specialized based on the individual survivor’s risk. For example, in breast cancer, in the general population, we know that early detection and screening for breast cancer is the most effective way to reduce the burden and improve outcomes for patients with breast cancer. This is because you get to pick up on it earlier and treat it, making it less debilitating and improving survival.

Girls and young women who receive radiation therapy for the treatment of lymphoma, if the radiation therapy is near the breast tissue—which it used to be for most female patients with Hodgkin lymphoma—as they get older, have an exceptionally high risk of developing breast cancer. [Additionally], when they develop breast cancer, it’s much earlier than when you would expect for the general population. Starting mammography for these individuals at or around the age of 40 years is too late. [Because of this risk], we use the same screening paradigm but modify it slightly. We perform [mammograms] for these high-risk childhood cancer survivors starting at the age of 25 years in conjunction with MRI of the breast tissue. This is because MRI picks up breast cancers in young women and complements the work of a mammogram.

We’ve used population-based screening approaches, but we target them based on the individual’s risk based on the treatment they received. We have similar recommendations for individuals who received radiation to their abdomen for the treatment of cancer that was in their abdominal area, as they have a much higher risk of developing colorectal cancer [CRC]. We don’t wait until the traditional general population age to start screening for CRC at 45 or 50 years; we start much earlier. These approaches have been important.

Many childhood cancer survivors experience a significant gap in care when transitioning from pediatric oncology to adult health care systems. What challenges contribute to this gap, and what steps can be taken to ensure continuity of care during this critical period?

Many children with cancer in the United States are treated in exclusively children’s cancer hospitals. I work at a hospital where we can take care of children, as well as adults. Based on my own experiences, the process of transition from childhood into adulthood [cancer care] is different based on the location. At a primarily children’s cancer–focused hospital, most of the care, screening, and follow-up after the cancer treatment is done at the children’s hospital. However, typically at or around 18 to 21 years of age, [patients are required to] transition to an adult facility. If there’s a partner adult facility, that’s great, but oftentimes there isn’t a partner adult facility that is willing to take on these long-term survivors.

The reason why it’s important to identify an appropriate bridge is because the time at which the patient is transitioning is the time when they’re at the highest risk of developing late effects of therapy. These include different cancers, cardiovascular issues, and bone issues. If that transition doesn’t happen smoothly and comprehensively, then many of these patients fall through the gaps. As a result of that, many of the health conditions they develop when they are in their 20s, 30s, and 40s are under diagnosed and not treated appropriately or not prevented.

They’re not undergoing the screenings that they should be going through. One [reason for this] is that children who become adults don’t have full understanding of what their cancer treatment was, and they don’t have a full understanding what their risks are. Therefore, it’s important to transition the childhood cancer survivor to an appropriate partner with all the information that they need. They need to know what their diagnosis was, the treatment they received, the screenings for late effects that they should be undergoing, and how often those screenings should be. They should have that in their hand as that transition is happening.

The other facet that’s missing is that when patients don’t go to an appropriate partner institution that has knowledge of survivorship issues, they end up in their primary care provider office as one of many hundreds of other patients. It’s hard for primary providers to keep track of this, so we try to educate them, but that’s a challenge. At the City of Hope Children’s Cancer Center, we have built a program where there is no age-out [point]. Oncologists can continue to see patients through childhood and into adulthood. We have built a unique platform where we can see patients for the rest of their life through healthy partnerships. More institutions are adopting that model when possible.

What recent innovations or trends do you find most promising for improving outcomes and reducing long-term adverse effects (AEs) for pediatric patients?

As a pediatric oncologist, this is the most exciting time that we have been in over the past 20 to 30 years. In the 1970s and 1980s, all the pediatric oncology institutions around the country came together to develop collaborative groups and cooperative groups and work together to find new ways, new combinations of therapies, to treat children with cancer. Because of that collaboration, we turned cancers that were otherwise incurable into highly curable cancers.

Today, more than 85% of children in general, are cured of their cancer, and that collaboration was a big milestone moment in pediatric oncology. I believe the next big milestone moment was us recognizing that not all pediatric cancers are the same, and that there are genetic markers we can use to help stratify patients and make decisions on treatment based on those genetic markers. We can risk stratify and tailor therapies, and that risk stratification based on genetic markers on the tumors themselves has been a game changer for many cancers, including brain tumors and other types of kidney tumors, for example. For hematologic malignancies like leukemias and lymphomas, these genetic markers have been important and have fundamentally changed how we think about patients, but they have also helped us develop new therapies that are less toxic than the traditional therapies.

[These genetic markers have] allowed us to remove some therapies when possible and replace them with immunotherapies, which are more targeted approaches to killing the cancer [that are associated] with fewer long-term AEs. These targeted approaches have allowed us to go from an 85% [cure rate] to an over 95% [cure rate] for some leukemias, including in the most common type of cancer in children. That is a remarkable advance that’s happened over the past approximately 10 years.