Whole-body MRI (WBMRI) screening of patients carrying the germline mutation in the TP53 tumor suppressor gene — the so-called Li-Fraumeni syndrome ― is warranted because the procedure detects enough new, localized primary cancers to justify its use, say researchers reporting new data, including a meta-analysis of multiple cohorts.
The meta-analysis was published online August 3 in JAMA Oncology, along with several related articles.
"Cancer screening in germline TP53 mutation carriers is especially challenging because of the wide spectrum of associated malignant neoplasms," write the authors, led by Mandy Ballinger, PhD, National Cancer Institute, Bethesda, Maryland.
"Baseline WBMRI identified new and treatable malignant neoplasms in as many as 7% of TP53 mutation carriers, confirming that this modality enables clinically useful early detection of cancer in this highly cancer-prone population across a broad range of health systems," they add.
The meta-analysis included 13 cohorts of patients from six countries. These cohorts were identified through the Li-Fraumeni Exploration Research Consortium.
A total of 578 participants, approximately two thirds of whom were female, underwent baseline WBMRI between January 2004 and October 2016.
Almost half of the participants had already been diagnosed with at least one prior malignancy.
WBMRI detected 42 malignant lesions in 39 individuals.
"Overall, 1 in 14 participants undergoing their first WBMRI was found to have a primary malignant neoplasm, which was then treated with curative intent," investigators note.
The false positive rate was 42.5%. Researchers defined the false positive rate as the proportion of suspected neoplasms that were either benign, a recurrence of a preexisting cancer, or a newly diagnosed metastatic cancer.
Cancer detection rates were higher among children and lowest among young adults, the researchers observe. Detection rates increased among older participants.
The investigators also noted that the incidence of brain tumors and bone sarcomas was higher in children, whereas epithelial malignant neoplasms were more likely to be detected in older adults.
"Our findings suggest that WBMRI may be a useful component of the routine baseline assessment of TP53 mutation carriers in children and adults," the investigators conclude.
Prospective Cancer Screening
A prospective cancer screening study conducted at the National Cancer Institute, which was published with the meta-analysis, confirms these findings.
Senior author Sharon Savage, MD, of the National Cancer Institute, and colleagues carried out baseline WBMRI in 116 patients with Li-Fraumeni syndrome.
In this study, patients also underwent brain and breast MRIs, mammography, colonoscopy, abdominal ultrasound examination, and blood testing.
In this cohort, 61.2% of participants had a history of at least one cancer prior to undergoing baseline screening.
"Abnormal MRI findings requiring additional follow-up were identified in 32 of the 116 WBMRIs (27.5%) performed," the researchers observe.
"We report a cancer detection rate of 6.9% at baseline screening among 116 individuals," they add. Of the eight individual cancers detected on baseline screening, half were detected by WBMRI alone.
None of the cancers detected on baseline screening were detected by colonoscopy, mammography, or bloodwork, the authors note.
Personalized prevention approaches like this are critical. Dr Sharon Savage
In this study, a false positive test was defined as any radiographic or laboratory test that required additional evaluation in participants who did not have cancer. The false positive rate in this study was 29.6%
"For high-risk populations, like families with LFS [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 said in a statement.
This protocol...offers patients with LFS a new road map for early cancer detection. Dr Sharon Savage
"This protocol, along with other published studies, offers patients with LFS a new road map for early cancer detection going forward," she added. "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."
Similar Data From France and Holland
In several research letters that were published in the same issue of JAMA Oncology, the authors reported their experience screening patients with Li-Fraumeni syndrome.
French investigators under lead author Olivier Caron, MD, Gustave Roussy Hopital Universitaire, Villejuif, France, report that they, too, used WBMRI to screen 107 individuals with the Li-Fraumeni syndrome. The patients are part of the LIFSCREEN randomized clinical trial being carried out in France.
Similar to the other reports, the French team note that almost half of patients in the LIFSCREEN study (48%) had a prior history of cancer.
So far, the investigators have detected 23 new primary cancers in 20 patients with WBMRI.
Ten of those cancers belong to what the authors describe as the "core" cancers on the Li-Fraumeni spectrum; the remaining 13 cancers were outside of this core spectrum. Of these, the most frequently detected was lung adenocarcinoma.
"The proportion and diversity of off-core LFS spectrum cancers detected in TP53 mutation carriers as reported by others give growing evidence of a broader LFS spectrum," the authors write.
"Our observations seem to support recent moves toward broader cancer screening in TP53 mutation carriers," they observe.
A Dutch group reports similar surveillance results from the Life-Guard study, which involves 56 carriers of the TP53 mutation. Life-Guard participants undergo annual surveillance that includes WBMRI.
Again, 48% of this group had had a prior malignancy.
Abnormal findings were detected on 32 WBMRIs in 24 patients. All 24 patients underwent additional imaging or referral.
Four of these abnormal screening results were found to be malignant (representing 12.5% of the total screened); 28 of the abnormal findings were false positive, yielding a false positive rate of 87.5%.
"The initial round of our annual surveillance program in patients identified as TP53 mutation carriers detected malignancies in approximately 7% of patients," the Dutch authors write.
They caution that there were multiple false positive findings that necessitated additional diagnostic workup in a large proportion of patients.
In a related commentary, Peter Asdahl, MD, PhD, from Aahus University Hospital, Denmark, and fellow editorialists also express concerns about the risk for false positive test results if patients with the Li-Fraumeni syndrome are subjected to routine surveillance.
"False positives and cancer overdiagnosis may result in psychological distress, radiation exposure from further diagnostic workup and the risks of unnecessary biopsy and surgery," the editorialists write.
Although it is important for expert groups to arrive at a consensus on the optimal approach to the Li-Fraumeni syndrome, "more evidence is needed, most urgently the evidence of reduction in cancer-related mortality associated with any screening technique," they caution.
None of the authors or editorialists have disclosed any relevant financial relationships.
JAMA Oncol. Published online August 3, 2017. Meta-analysis, full text; NCI study, abstract; French report, abstract; Dutch report, abstract; Commentary, abstract