Whole-body MRI detects early cancers in Li-Fraumeni syndrome

Whole-body MRI increased detection of abnormalities and new cancers in patients with Li-Fraumeni syndrome, according to results of two studies published in JAMA Oncology.

Li-Fraumeni syndrome is a rare hereditary disorder linked to the TP53 gene that often results in various cancers, including breast cancer, sarcoma and brain tumors.

“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,” Sharon A. Savage, MD, chief of the clinical genetics branch in the division of cancer epidemiology and genetics at NCI, said in a press release. “This protocol, along with other published studies, offers patients with Li-Fraumeni syndrome a new road map for early cancer detection going forward.”

No universally accepted strategies for care exist. Thus, early detection is crucial for patients.

Intensive cancer surveillance

In one study, Savage and colleagues sought to determine the feasibility and efficacy of a comprehensive cancer screening protocol in patients with Li-Fraumeni syndrome using multiple radiologic techniques, such as whole-body MRI and laboratory measurements.

The analysis included data from 116 individuals (66.4% female; median age, 37.6 years; range, 3-68) with Li-Fraumeni syndrome and a germline TP53 variant who underwent baseline evaluation at the NCI or NIH between June 2012 and July 2016.

Patients aged 3 to 16 years underwent annual rapid whole-body MRI, brain MRI, physical examination and blood tests every 4 months. Patients aged 16 years and older followed the same screening protocol, with the addition of colonoscopy every 3 years beginning at 25 years; annual breast MRI with optional mammography among women aged 20 to 40 years; and mandatory annual breast MRI and mammography among women aged older than 40 years.

Nearly two-thirds of individuals (61.2%) had previous cancer diagnoses, but no patient had received active cancer therapy at least 6 months prior to screening.

Overall, 34% of individuals (n = 40) had abnormalities at baseline screening examination with whole-body, brain or breast MRI. Of these, 32 were incidental, benign or normal findings resulting in a false-positive rate of 29.6%.

Eight patients received diagnoses of new primary cancers, including lung adenocarcinoma, preinvasive breast cancer (n = 2 each), osteosarcoma, sarcoma, astrocytoma and low-grade glioma (n = 1 each).

Baseline blood tests, abdominal ultrasonography in children, mammography and colonoscopy did not lead to a diagnosis of prevalent cancer.

Meta-analysis

Savage and colleagues also conducted a meta-analysis of cohorts that incorporated whole-body MRI for individuals with germline TP53 mutations from January 2004 to October 2016 to assess the clinical utility of whole-body MRI in these patients.

The researchers identified 13 clinical and research surveillance cohorts with 578 individuals (65.1% female; mean age, 33.2 years; standard deviation, 17.1 years) through the Li-Fraumeni Exploration Research Consortium. Among the individuals included in the analysis, 48.4% had received previous diagnoses of at least one prior malignant neoplasm.

Rapid whole-body MRI had a detection rate of 7% (95% CI, 5-9) for new primary cancers. Researchers diagnosed 225 lesions deemed benign or malignant neoplasms in 54 patients. Forty-two cancers — 35 categorized as new localized cancers treated with curative intent — occurred in 39 patients.

“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,” Savage said.

Risks and benefits

The studies by Savage and colleagues show that detecting early resectable cancer is possible among individuals with Li-Fraumeni syndrome, Peter H. Asdahl, MD, PhD, from the department of hematology at Aarhus University Hospital in Denmark, and colleagues wrote in a related editorial. However, limitations need to be addressed before whole-body MRI can be universally recommended.

“False positives and cancer overdiagnosis may result in psychological distress, radiation exposure from further diagnostic workup and the risks [for] unnecessary biopsies and surgery,” Asdahl and colleagues wrote. “The risks and benefits of this screening strategy are largely unknown.”

The clinical community and advocacy groups are requesting consensus statements from patients with Li- Fraumeni and other syndromes to determine the most optimal care; however, more efforts are needed, they wrote.

“More evidence is needed, most urgently the evidence of reduction in cancer-related mortality associated with any screening technique,” Asdahl and colleagues wrote, adding that large-scale cooperation and innovative clinical trials would enhance efforts. – by Melinda Stevens

References:

Asdahl PH, et al. JAMA Oncol. 2017;doi:10.1001/jamaoncol.2017.2459.

Ballinger ML, et al. JAMA Oncol. 2017;doi:10.1001/jamaoncol.2017.1968.

Mai PL, et al. JAMA Oncol. 2017;doi:10.1001/jamaoncol.2017.1350.

Disclosure s : The researchers and Asdahl and colleagues report no relevant financial disclosures.