Early Surveillance in Pediatric Patients Genetically Predisposed to Cancer

Initiating surveillance soon after recognizing a pediatric patient has a genetic predisposition for cancer may improve the identification of early-stage asymptomatic tumors, according to a recent study published by Blake et al in JAMA Oncology. The findings may inform clinical practice following genetic testing.

Background

Recent advances in genomic sequencing have revealed that 5% to 15% of pediatric patients with cancer may have an underlying genetic predisposition. Although genetic predispositions can increase the risk of developing new tumors, it is currently unclear when to begin surveillance for these tumors—since data on its effectiveness and outcomes are sparse. Conventional practice typically results in surveillance that begins months to years after detecting a genetic predisposition.

Historically, it has been challenging for physicians to persuade insurance companies to cover early screenings. This created a cycle in which physicians were unable to order tests, providing no strong evidence of their value and preventing their use.

“We’ve shown that following standardized surveillance protocols provides a very effective way to detect new tumors at their earliest and most treatable stages,” emphasized senior study author Kim Nichols, MD, Director of the Department of Oncology in the Division of Cancer Predisposition at the St. Jude Children’s Research Hospital. “Understanding whether children have an underlying genetic risk for cancer can greatly impact their clinical care, and proactive surveillance for new tumors is an important component of this care,” she continued.

Study Methods and Results

In the recent study, the researchers examined 274 pediatric patients with 35 different cancer-predisposing conditions. After a median follow-up of 3 years, the researchers used surveillance to reveal tumors in 27 of the patients, representing a broad array of solid and central nervous system neoplasms. To detect potential tumors and guide treatment, physicians used various surveillance methods—including annual full-body magnetic resonance imaging among patients with a predisposition for solid tumors. Standard surveillance methods had minuscule false-positive and false-negative rates.

“Overall, across these different reports and reviews of the relevant images, there was an excellent performance of the different modalities. We had very few false-positive or -negative findings, meaning we did not need to pursue unnecessary interventions or miss any incipient tumors. Both factors are essential in optimizing the care for our patients with underlying predispositions,” detailed Dr. Nichols.

Notably, most of the new cancers detected in the study were found using early surveillance just after the genetic predisposition was discovered. Nearly 33% of the tumors were detected at the first surveillance intervention soon after diagnosis, and about 67% of them were detected within 2 years of the initial surveillance visit. This included a small subset of patients already being treated for a different cancer type.

“About 17% of the children had a new tumor identified while they were still undergoing treatment for a prior cancer,” Dr. Nichols stressed. “Often, [health-care] providers wait until a [patient] has finished treatment for their first cancer before they start screening for other potential malignancies. If [they] do that, it is possible [they’ll] miss a new tumor. [Health-care] providers should now recognize the importance of starting the recommended surveillance tests the moment they discover an underlying predisposition,” she suggested.

Initiating surveillance immediately also resulted in finding cancers in their earlier stages. Without the early screening, the researchers hypothesized that many of the tumors would have remained undetected until much later, because almost all of them were asymptomatic at the time of discovery. By finding these tumors at an early stage, physicians were able to completely remove about 50% of early-stage asymptomatic tumors through surgical resection alone. Avoiding the need for toxic chemotherapies or radiation therapies may prevent long-term treatment-related side effects, a significant consideration when treating pediatric patients. Additionally, around 70% of the tumors were entirely removed without leaving microscopic traces behind. 

“We were able to remove these tumors without any evidence of disease left behind. These patients will have better outcomes and may need less or even no chemotherapy or radiation therapy,” Dr. Nichols highlighted.  

Conclusions

The research demonstrated the benefit of early surveillance applied across multiple cancer types and predisposing conditions. The researchers hope their findings enable more physicians to order these effective, yet sometimes expensive, tests. The excellent performance of the standard screening methods offered evidence that early testing may improve the detection of early-stage asymptomatic tumors and patient outcomes. This may give insurance companies the evidence needed to cover the tests for pediatric patients with genetic predispositions. 

“I hope that providers will initiate recommended surveillance as soon as they learn that someone has an underlying predisposition,” Dr. Nichols underscored. “They shouldn’t hesitate to start looking as soon as they learn about the predisposition, and it’s imperative to follow through with that surveillance. Then, we can find these tumors early, while they are potentially easier to treat,” she concluded.

Disclosure: The research in this study was supported by grants from the American Lebanese Syrian Associated Charities. For full disclosures of the study authors, visit jamanetwork.com.