Clinical characteristics and management of Li-Fraumeni syndrome-associated lung cancer.

Pathogenic germline TP53 variants predispose to lung adenocarcinoma, associated in this series with activating EGFR alterations.

Li-Fraumeni syndrome, caused by pathogenic germline TP53 variants, is increasingly recognised as a predisposition to lung adenocarcinoma, whose clinical features remain poorly defined. The authors retrospectively reviewed patients followed for Li-Fraumeni syndrome at their institution between 2000 and 2025 and identified five primary lung adenocarcinomas among 32 affected individuals. Median age at diagnosis was 34 years (range 29-53), four patients had never smoked, three had a family history of lung cancer and three had multiple synchronous lung lesions; an activating EGFR alteration was found in all four patients tested. The clinical course was heterogeneous, with ongoing disease control on lazertinib plus amivantamab in one patient with advanced disease, 34 months on gefitinib then 51 months on osimertinib after acquisition of EGFR T790M in another, and curative-intent surgery after surveillance detected two early-stage cancers; two of the five patients did not fulfil the 2015 Chompret criteria.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Two points are directly usable in clinic: do not attribute a lung adenocarcinoma in a young never-smoker to chance in a suggestive family, and bear in mind that surveillance here caught two tumours at an operable stage. What is not usable is the frequency of EGFR alterations, four of four tested: the figure comes from a selected series of five patients and cannot be presented as a feature of Li-Fraumeni-associated lung cancer. The most interesting signal is that two of five patients fell outside the Chompret criteria, a further argument for germline testing driven by phenotype rather than family history alone.

Analysis by Dr Thibaut Benquey