Guidelines help identify inherited risk in childhood cancer survivors

The last day of active treatment is an important milestone for children treated for cancer. However, for some survivors, the risk of developing another cancer remains even after treatment ends, making continued monitoring an important part of their long-term care.

Up to 12% of childhood cancer survivors have an underlying cancer predisposition syndrome, a genetic condition that increases their risk of developing cancer. Identifying these conditions can help clinicians determine which survivors may benefit from additional cancer surveillance, genetic counseling and other preventive measures.

“Identifying an underlying cancer predisposition can help explain why a child developed cancer in the first place,” said Kim Nichols, MD, Division of Cancer Predisposition director in the Department of Oncology. “It can also reveal an increased risk of developing other cancers later in life, allowing us to implement cancer surveillance or risk-reducing interventions.”

Despite these benefits, guidance on which childhood cancer survivors should be referred for genetic evaluation has historically been limited. To address this gap, Nichols and colleagues developed recommendations that were incorporated into the Children’s Oncology Group (COG) Long-Term Follow-Up Guidelines. Nichols is a co-senior author of a policy review published in The Lancet Oncology that describes the development of the recommendations, which aim to improve the identification of inherited cancer risks and inform long-term survivorship care.

Recognizing genetic risk beyond the initial diagnosis

While genetic testing has become increasingly integrated into the care of children newly diagnosed with cancer, genetic evaluation has historically received less attention during survivorship. As a result, some survivors may have completed treatment without ever being assessed for an underlying cancer predisposition syndrome. Others may not have met genetic testing criteria at diagnosis but could benefit from later evaluation as their personal or family medical history changes.

The COG Long-Term Follow-Up Guidelines have helped clinicians monitor survivors for late effects associated with cancer treatment; however, the guidelines previously lacked recommendations for identifying survivors who may have an underlying genetic predisposition to cancer.

“Once a patient gets beyond the initial diagnosis and enters survivorship, providers may not think about hereditary cancer,” Nichols said. “But identifying an underlying genetic predisposition is important because it can help us determine who needs additional screening to detect new cancers at their earliest and most treatable stages.”

Recognizing this gap, Nichols and colleagues examined the literature about inherited cancer-predisposing genetic alterations in childhood cancers. They arrived at expert consensus to establish recommendations to help clinicians determine which survivors should be referred for genetic evaluation. The recommendations provide a standardized framework for identifying those survivors who may benefit from referral for genetic counseling and testing, considering factors such as diagnosis, personal and family cancer history, and other clinical characteristics. These factors can help clinicians recognize when genetic counseling may be warranted, even years after a survivor’s initial diagnosis. 

Supporting continuity of care for childhood cancer survivors 

Identifying an underlying cancer predisposition syndrome can have important implications for a survivor’s long-term care. For those with increased genetic risk, clinicians can tailor surveillance to detect subsequent cancers earlier, consider preventive measures and make treatment decisions that account for potential inherited susceptibilities. 

“Adult healthcare providers are often more familiar with hereditary cancer syndromes that manifest in adulthood, such as hereditary breast and ovarian cancer,” said Nichols. “Because childhood cancers are not generally seen in adult practice, providers may be less familiar with the genetic predisposition syndromes associated with them. Nevertheless, this information is important for adult survivors of childhood cancer as they plan their own families. Further, for some survivors, cancer risks may extend across the lifespan and into adulthood.” 

These differences underscore the importance of incorporating genetic risk information into long-term follow-up care. The guidelines also provide a resource to support continuity of care, helping clinicians recognize inherited cancer risks and maintain appropriate surveillance as survivors transition between providers. 

Expanding awareness and access to genetic evaluation 

Integrating the guidelines into routine survivorship care may face challenges, including limited access to genetic counselors, insurance coverage and financial barriers. The policy review highlights several approaches to improving access, including incorporating genetic counseling into survivorship clinics, coordinating appointments and expanding telehealth services. 

Increasing awareness and adoption of the guidelines among clinicians will be essential to addressing a longstanding gap in survivorship care. By establishing clear criteria for referral, the recommendations aim to make genetic risk assessment a more consistent part of long-term follow-up for childhood cancer survivors — a population that is growing.  

“I hope that these guidelines will facilitate the incorporation of genetic evaluation as a routine part of survivorship care,” said Nichols. “We want clinicians to recognize when a survivor may have an underlying cancer predisposition so that those at increased risk can receive genetic counseling, testing, and the screening and follow-up care needed to improve their overall health outcomes.”