Classic Li-Fraumeni syndrome criteria are as follows
[2] :
-
A proband diagnosed with a sarcoma before age 45 years
and
-
A first-degree relative with any cancer diagnosed before age 45 years
and
-
Another first- or second-degree relative with any cancer
diagnosed before age 45 years or a sarcoma diagnosed at any age
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
abstract:
Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: 11 year follow-up of a prospective observational study - The Lancet Oncology
Background
Carriers of a germline
TP53
pathogenic variant have a substantial lifetime risk of developing
cancer. In 2011, we did a prospective observational study of members of
families who chose to either undergo a comprehensive surveillance
protocol for individuals with
Li-Fraumeni syndrome or not. We sought to
update our assessment of and modify the surveillance protocol, so in
this study we report both longer follow-up of these patients and
additional patients who underwent surveillance, as well as update the
originally presented surveillance protocol.
Methods
A
clinical surveillance protocol using physical examination and frequent
biochemical and imaging studies (
consisting of whole-body MRI, brain
MRI, breast MRI, mammography, abdominal and pelvic ultrasound, and
colonoscopy) was introduced at three tertiary care centres in Canada and
the USA on Jan 1, 2004, for carriers of
TP53 pathogenic variants. After confirmation of
TP53
mutation, participants either chose to undergo surveillance or chose
not to undergo surveillance. Patients could cross over between groups at
any time. The primary outcome measure was detection of asymptomatic
tumours by surveillance investigations. The secondary outcome measure
was 5 year overall survival established from a tumour diagnosed
symptomatically (in the non-surveillance group) versus one diagnosed by
surveillance. We completed survival analyses using an as-treated
approach.
Findings
Between Jan 1, 2004, and July 1, 2015, we identified
89 carriers of
TP53
pathogenic variants in 39 unrelated families, of whom 40 (45%) agreed
to surveillance and 49 (55%) declined surveillance. 19 (21%) patients
crossed over from the non-surveillance to the surveillance group, giving
a total of 59 (66%) individuals undergoing surveillance for a median of
32 months (IQR 12–87).
40 asymptomatic tumours have been detected in 19
(32%) of 59 patients who underwent surveillance. Two additional cancers
were diagnosed between surveillance assessments (false negatives) and
two biopsied lesions were non-neoplastic entities on pathological review
(false positives).
Among the 49 individuals who initially declined
surveillance, 61 symptomatic tumours were diagnosed in 43 (88%)
patients. 21 (49%) of the 43 individuals not on surveillance who
developed cancer were alive compared with 16 (84%) of the 19 individuals
undergoing surveillance who developed cancer (p=0·012) after a median
follow-up of 46 months (IQR 22–72) for those not on surveillance and 38
months (12–86) for those on surveillance.
5 year overall survival was
88·8% in the surveillance group and 59·6% in the non-surveillance group.
Interpretation
Our
findings show that long-term compliance with a comprehensive
surveillance protocol for early tumour detection in individuals with
pathogenic
TP53 variants is feasible and that early tumour
detection through surveillance is associated with improved long-term
survival. Incorporation of this approach into clinical management of
these patients should be considered.
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