Abstract 3316: Screening blood tests and cancer detection in Li-Fraumeni syndrome
Authors: Oba Leatrisse , Loud Jennifer T. , Achatz Maria I. , Savage Sharon A. , Khincha Payal P. 
Published: August 2019

Li-Fraumeni syndrome (LFS) is an autosomal dominant cancer predisposition syndrome, caused primarily by germline pathogenic TP53 variants and associated with a very high lifetime cancer risk which reaches approximately 100% by age 60 years. Individuals with LFS are also at significant risk of developing multiple primary cancers. Current comprehensive cancer screening recommendations in LFS include annual whole-body MRI, brain MRI, breast MRI (for women), and bloodwork (complete blood count, erythrocyte sedimentation rate, lactate dehydrogenase level) every 3-4 months for the detection of hematological malignancies. Additionally, children undergo 3-4 monthly abdominal ultrasound and hormonal testing (serum progesterone, testosterone, DHEAS,dehydroepiandrostenedione, androstenedione, alpha fetoprotein and beta-human chorionic gonadotropin levels) for detection of adrenocortical carcinomas and germ cell tumors. While this screening is effective in early cancer detection, it adds to the psychosocial burden of LFS.

We evaluated the benefit of 4-monthly blood work in 139 participants of the National Cancer Institute’s IRB-approved longitudinal cohort screening study (NCT01443468, http://lfs.cancer.gov) between 2012 and October 2018. All participants underwent annual screening at the NIH Clinical Center; 3-4 monthly bloodwork and pediatric ultrasounds were coordinated with their healthcare providers. The cohort included 89 females (64%) and 50 males (36%). Twenty-six patients (19%) were of children at enrollment, and 113 (81%) were adults. The median age at baseline screening was 35 years (range 1-68), with a median annual screening of 4 visits (range 1-7). The median follow-up time was 35 months (range 3-72) and median number of quarterly screening bloodwork was 9 (range 1-18). Seventy-two of 1248 total blood tests (6%) were missed due to non-compliance or medical reasons. Of the 139 patients, 33 (24%) developed 45 screen-detected or interval cancers during their study participation. Of the 45 cancers detected, only one (2%), a colorectal cancer, was detected with screening bloodwork due to a down-trending hemoglobin that led to colonoscopy. No hematological malignancies, adrenocortical carcinomas or germ-cell tumors were detected as a result of blood screening. One female participant was diagnosed with polycythemia vera after identification of persistent thrombocytosis. One adult male was diagnosed with iron-deficiency anemia requiring iron infusions due to persistent anemia. Eight additional abnormal tests required follow-up bloodwork, all of which were within the normal range.

Our data suggest that quarterly screening blood tests may not independently add to the benefit of radiological screening in LFS. Longitudinal follow-up and detailed analyses are underway to determine the appropriate screening interval in individuals with LFS.

Citation Format: Leatrisse Oba, Jennifer T. Loud, Maria I. Achatz, Sharon A. Savage, Payal P. Khincha. Screening blood tests and cancer detection in Li-Fraumeni syndrome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3316.