In a new study from the National Cancer Institute (NCI), researchers found a higher-than-expected prevalence of cancer at baseline screening in individuals with Li-Fraumeni syndrome, a rare inherited disorder that leads to a higher risk of developing certain cancers. The research demonstrates the feasibility of a new, comprehensive cancer screening protocol for this high-risk population.
The study was led by Sharon A. Savage, MD, of NCI’s Division of Cancer Epidemiology and Genetics (DCEG), and was published in JAMA Oncology.
About Li-Fraumeni Syndrome
Li-Fraumeni syndrome is most often caused by germline mutations in the tumor-suppressor gene TP53. The disorder results in many kinds of cancers—including sarcomas, breast cancer, brain tumors, and cancer of the adrenal gland—that frequently occur at young ages. Individuals with Li-Fraumeni syndrome have an approximately 50% chance of developing cancer by age 40, and up to a 90% chance by age 60. Many patients with the disorder develop more than one primary cancer over their lifetimes.
Frederick Pei Li, MD, and Joseph F. Fraumeni, Jr, MD, first described Li-Fraumeni syndrome at the NCI in 1969. “Researchers at the NCI have evaluated families with Li-Fraumeni syndrome extensively to better understand how germline mutations in TP53 influence risk and how best to prevent cancers or treat them at the earliest possible stage,” said Dr. Fraumeni, Scientist Emeritus and Founding Director of DCEG. “However, because of the broad spectrum of cancers in Li-Fraumeni syndrome families, it has been challenging to put in place universally accepted cancer strategies.”
To address this gap in clinical care, researchers modified a cancer surveillance protocol from a previously published study and screened 116 Li-Fraumeni syndrome patients with germline TP53 mutations using a variety of tools including whole-body, brain, and breast magnetic resonance imaging (MRI), as well as mammography, colonoscopy, bloodwork, and abdominal ultrasound. The study only used modalities that do not utilize ionizing radiation for imaging, since patients with Li-Fraumeni syndrome appear to be radiosensitive.
They found that 40 trial participants (34%) had abnormalities on baseline screening examination with whole-body, brain, or breast MRI that required further evaluation. Eight of these patients (7%) were diagnosed with a new primary cancer. All but one of the cancers found through screening were fully removed with surgery. In contrast, the non-MRI techniques used in the trial did not lead to a diagnosis of cancer at baseline screening.
“For high-risk populations, like families with Li-Fraumeni syndrome, personalized prevention approaches like this are critical to the early detection of the many kinds of cancers seen in this group,” Dr. Savage explained. “This protocol, along with other published studies, offers patients with Li-Fraumeni syndrome a new road map for early cancer detection going forward.”
The meta-analysis, published by Ballinger et al in JAMA Oncology, involved 578 participants with Li-Fraumeni syndrome in 13 cohorts at multiple research centers around the world. Similarly utilizing rapid whole-body MRI, the investigators had an overall detection rate of 7% for new primary cancers, confirming the results of the study conducted at the NCI.
“The findings from this international team effort further demonstrate the utility of whole-body MRI screening for individuals with Li-Fraumeni syndrome,” Dr. Savage said. “With long term follow-up, additional refinement, and through international collaborations, we hope to establish a screening regimen that could extend and improve the lives of this unique population.”
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.