Radiotherapy and secondary malignancies in patients with Li-Fraumeni syndrome: a systematic review and meta-analysis

Keywords

Oncogenetics - Li-Fraumeni Syndrome - TP53 mutation

Introduction: Li-Fraumeni (LFS) and Li-Fraumeni-like (LFL) syndromes are rare genetic conditions associated with a heightened susceptibility to cancer development, stemming from germline mutations in the TP53 tumor suppressor gene. Prior studies highlighted an increased risk of secondary malignancies linked to radiotherapy (RTx). Here, we present the first systematic review with a meta-analysis evaluating the therapeutic effectiveness and the incidence of secondary malignancies in patients with pathogenic variants of TP53 who have undergone RTx.

Methods: We systematically searched Pubmed, Cochrane, and EMBASE databases until April 2024. Prospective and retrospective studies examining the effects of radiotherapy (RTx) in patients with Li-Fraumeni syndrome (LFS) were eligible for inclusion. We pooled the prevalence of radio-induced malignancies (RIM), total recurrence (TR), and other second primary malignancies (SCM), along with their respective 95% confidence intervals (95% CI). Statistical analyses were carried out using R software version 4.3.2, and heterogeneity was assessed using I² statistics.

Results: Out of 1291 studies identified, 10 studies involving 254 patients met the inclusion criteria, with 183 of these patients having received radiation therapy during their treatment. The prevalence of RIM in patients previously treated with radiation therapy was found to be 23.54% (95% CI 14.47-35.90). The risk ratio for TR (including local and distant recurrences) was 2.32 (95% CI 0.90-5.95). Additionally, the risk ratio for SPM was 1.73 (95% CI 0.84-3.60) in the radiation therapy group.

Conclusions: While the prevalence of radio-induced malignancies (RIM) in patients with Li-Fraumeni syndrome who underwent radiotherapy is noteworthy, the risk ratios for total recurrence (TR) and secondary primary malignancies (SPM) were not statistically significant. This suggests that the association between radiotherapy and increased risks of TR and SPM remains uncertain. Further research is needed to clarify these risks and to guide personalized treatment and long-term surveillance in this high-risk population.

Corresponding author: João Pedro de Lima de Oliveira (e-mail: [e-mail]).

 

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No conflict of interest has been declared by the author(s).

Publication History

Article published online:
06 May 2025