Surveillance imaging and early surgical intervention for improved CNS tumor outcomes in children with Li-Fraumeni syndrome: Children's National Hospital experience and literature review

Abstract

Objective: Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by germline mutations in the TP53 gene. CNS tumors are the fourth most common tumor type in LFS, and recent screening guidelines demonstrate that early tumor detection is associated with improved long-term survival. However, there is a paucity of data regarding surgical intervention when lesions are identified in asymptomatic patients on surveillance imaging. The authors investigated this through their cohort and literature review.

Methods: The cohort consisted of children seen in the Pediatric Cancer Genetics Program at Children's National Hospital between August 2012 and August 2021. The authors also include a PubMed (MEDLINE) literature search of articles from 2006 to 2021 related to surveillance and CNS tumors in patients with LFS. Studies in which CNS tumors were not identified or detailed patient information was not provided were excluded. Patients from the selected articles and the authors' cohort were added for further analysis.

Results: Between August 2012 and August 2021, 10 children with LFS and CNS tumors were assessed at Children's National Hospital: 4 who were known carriers of the TP53 mutation had CNS lesions found on surveillance imaging, whereas 6 presented with symptomatic CNS lesions and were either known or subsequently found to have germline TP53 mutations. The literature search identified 148 articles, 7 of which were included in this review. Patients from the literature and the present cohort were added for a total of 56 CNS lesions. A majority of the low-grade CNS lesions (22/24, 92%) were found on surveillance protocols in asymptomatic patients, whereas the majority of the high-grade lesions (22/26, 85%) presented in symptomatic patients who were not undergoing routine surveillance or as the initial diagnosis of LFS. The authors noted a significant survival advantage in pediatric patients with low-grade lesions, with an overall survival of 100% at 30 months. Minor limitations of the study include patient sample size and limitations in the patient cohort due to this being a retrospective rather than a prospective study.

Conclusions: Data presented in this study support surveillance protocols in LFS and demonstrate the importance of dedicated CNS imaging and early surgical intervention when lesions are identified. Systematic review registration no.: CRD42022372610 (www.crd.york.ac.uk/prospero).

Keywords: Li-Fraumeni syndrome; brain tumor; oncology; screening.

FIG. 1.

Pathology and radiology images. Axial T2 FLAIR MRI obtained in the patient in case 2 showing a right frontal mass before (A) and after (B) surgery. Pathology was consistent with a diffuse LGG on H&E-stained sections (C; bar = 0.1mm) with low Ki-67 proliferative index (D; bar = 0.05mm). The patient in case 5 had a large right frontal/parietal mass with associated edema and midline shift (arrow) seen on coronal T1-weighted MRI obtained with contrast before (E) and after (F) surgery. H&E-stained sections showed an embryonal tumor (G; bar = 0.1 mm) with high Ki-67 proliferative index (H; bar = 0.1 mm). Axial T2-weighted fast spin echo (I) and FLAIR (J) images demonstrating a right parietal/supramarginal lesion in the patient in case 6 (white arrows indicate tumor location). H&E-stained sections showed high-grade neuroepithelial tumor (K; black arrows pointing to mitotic figures, bar = 0.05mm) with high Ki-67 proliferative index (L; bar = 0.1mm).g

FIG. 2.

Flowchart depicting reports that were identified on the initial PubMed search, number of reports screened, number sought for retrieval, number excluded based on criteria defined above, and those included in the review.

FIG. 3.

Kaplan-Meier survival curves. A: OS for all patients included in the analysis. B: OS of patients presenting with symptoms (Sxns) (blue line) compared to those with tumors found on screening imaging (red line). C: Survival differences in pediatric (< 21 years of age) patients presenting with CPC (red line), embryonal (Embry) tumors (green line), HGGs (blue line), and LGGs (purple line). D: OS differences between females who are diagnosed based on screening MRI (F MRI, red line), or on symptoms (F Sxns, green line) and males who are diagnosed based on screening MRI (M MRI, blue line) or on symptoms (M Sxns, purple line).