Understanding common challenges in childhood cancer treatment

Lorna Rothery interviewed Dr John Glod from the National Cancer Institute, which is part of the National Institutes of Health, about the main challenges in childhood cancer treatment and the advancements in care

What are some of the key challenges associated with childhood cancer research, and how has this impacted the development of targeted treatments?

One of the well-known challenges in childhood cancer research is that these cancers are rare. This rarity makes it difficult to develop effective treatment strategies for children with cancer and to design clinical trials that can accommodate such uncommon diseases. A major issue is how to recruit enough patients for a trial to ensure that the results are statistically significant.

Additionally, cancers that occur in adolescents and young adults often have only a small proportion of cases within these age groups, complicating research even further. This age group falls in between pediatric and adult cancer care, making it a vulnerable population.

Collaborative efforts have been key in addressing these challenges. Larger groups that consist of multiple centers work together to recruit patients for the same trial. In the US, for example, organizations like the Children’s Oncology Group play a crucial role, and there are similar groups in Europe and other parts of the world.

We have made some progress over the last decade in including children in trials that are primarily designed for adults as long as the disease is biologically similar. The FDA has played an instrumental role in facilitating and encouraging clinical trials that include participants as young as 12 years old. This approach has allowed us to introduce effective cancer treatments more rapidly for pediatric patients, compared to the traditional method of first conducting trials in adults and then trying to initiate separate trials for children, which can be time-consuming and challenging due to the smaller number of pediatric patients.

Another significant challenge is that the limited number of pediatric patients may make the development of drugs specifically for this age group less attractive, as the market for these drugs is relatively small. Fortunately, both the European Medicines Agency (EMA) and the FDA have implemented measures to incentivize pharmaceutical companies to conduct studies and investigate drugs relevant to children.

What are the potential risk factors for cancer development in children?

The environmental risk factors for pediatric cancer are still not well-defined. For instance, radiation exposure, such as that experienced by children during the Chernobyl disaster, has been linked to a higher risk of thyroid cancer. However, aside from this, environmental risk factors remain largely unclear. Researchers are investigating various environmental exposures, including those in parents, but so far, no definitive environmental cause has been identified for most pediatric cancers.

Recently, we have come to realize that there may be a higher incidence of underlying cancer predisposition syndromes in children who develop cancer. Depending on the study, estimates suggest that up to 10% of children diagnosed with cancer have known genetic risk factors. We still do not fully understand the genetic factors that contribute to cancer risk in children, but they may be more significant than we previously thought. This information has emerged only recently.

What are some of the side effects and late effects of childhood cancer treatment?

That’s a really important question. As treatments for pediatric cancer have improved, one key consideration is how these therapies impact the long-term quality of life for children as they grow older. There are significant late effects associated with pediatric cancer treatment. These effects can be observed across almost all organ systems and vary depending on the treatment received.

One of the critical issues is the risk of infertility, which can be quite high with many pediatric cancer treatments. Additionally, the impact on normal childhood development is notable; these children often miss a significant amount of school, and their regular activities are disrupted for several years, which can affect their ability to engage in typical developmental activities. This includes establishing relationships and developing a sense of self.

Moreover, there are neurocognitive effects that are becoming more clearly understood, and these vary by type of cancer. Late effects can also influence heart function, lung health, bone density, and nearly any other organ system. We now have a greater understanding of these late effects, thanks to studies that outline the more common late effects and the timelines for when they may occur after treatment.

There are now better guidelines for monitoring these patients into adulthood, allowing us to be vigilant for any late effects and to treat them more promptly as they arise. Several studies and various approaches also aim to reduce the risk of late effects. These studies can be challenging because the occurrence of late effects in an individual are often not apparent until a long time after treatment. Additionally, some medications can be incorporated into chemotherapy regimens to help protect patients. Overall, I think there has been considerable progress in this area, and it’s a focus that many people are aware of and actively working on.

Are there any other notable developments in the world of childhood cancer treatment and research that you think our readers should be more aware of?

There is considerable work being done in pediatric cancer research, and significant advancements have been made in various therapies. Similar to adult cancer immunotherapies, I believe we are only beginning to explore the potential of immunotherapies for treating pediatric cancers, particularly leukemia and lymphoma.

Our understanding of very rare pediatric cancers is improving thanks to initiatives aimed at collaboration and knowledge accumulation for these unique patient groups. We are working to learn how existing treatments can be improved and to develop studies that can benefit those with rare cancers.

One notable effort is the National Cancer Institute (NCI), My Pediatric and Adult Rare Tumor Network (MyPART), supported by the Cancer Moonshot, which has seen great success and taught us much. Additionally, the NCI-coordinated Childhood Cancer Data Initiative. aims to collect data from every child in the US with cancer, including clinical imaging and pathology, and enhance sharing and access to this data. This effort will also include a national registry for very rare pediatric, adolescent, and young adult cancers. These efforts and others will enhance our understanding of the natural history of these diseases and their molecular biology and hopefully lead to new discoveries and effective treatments for these young patients with cancer.

When you consider that individual centers might only see one patient with a rare cancer every five to ten years, meaningful progress relies on pooling knowledge and experiences from various sources. These collaborative efforts have already significantly impacted pediatric cancer research and treatment.