Dados do Trabalho

Título

A RARE CASE OF SYNCHRONOUS LUNG ADENOCARCINOMAS WITH NF1 AND MET MUTATIONS

Apresentação do caso

A 62-year-old male, former-smoker (8 pack-years), had COVID-19 with respiratory symptoms in Dec 2020. A chest CT scan was performed during evaluation and an irregular nodule of 28 x 20 mm was detected at the upper left lobe. In Feb 2021, PET-CT showed a 42 x 25 mm mass at that same location (SUV 11.5) and a ground-glass nodular opacity of 27 x 14 mm at the right upper lobe (SUV 8.3). Left lung mass was an adenocarcinoma (PD-L1 negative, EGFR/ALK/ROS1/BRAF WT and insufficient material for other tests) and the right lung nodule was also an adenocarcinoma (NGS with MET exon 14 skipping mutation, ATM V1268, ARID1A Q546). Video mediastinoscopy found pleural implants on the left thorax, which histopathological analysis confirmed metastatic adenocarcinoma (NGS with NF1 K205 and NF1 K810). The patient is currently being treated with carboplatin, pemetrexed and pembrolizumab.

Discussão

Tumor suppressor gene neurofibromin 1 (NF1) is a RAS-MAPK pathway regulator. NF1 mutations are reported in a variety of cancers, including 8.3% of lung adenocarcinomas and 12% of lung SCC. They are more common in men and smokers, with unknown clinical significance. Concurrent driver mutations can occur, especially with genes related to MAPK/ERK signaling. 12.4% of 1062 lung cancer patients from a retrospective real-world study had a NF1 mutation, 30% of them with co-occurring mutations. Of these NF1-mutated patients, 51% received only one line of therapy, half of them with platinum-based chemo. 2nd and 3th lines were mostly anti-PD-(L)1 therapies. For 1st line, median real-world PFS was 124 days and median OS was 321 days, both shorter than described for other lung cancer mutations. NF1 mutations are related to chemo and targeted therapies resistance, but trials suggest that targeting MEK or mTOR could be effective. MET exon 14 skipping mutations are found in 3-4% of NSCLCs, mainly in adenocarcinoma and are frequently mutually exclusive. MET has shown to be a worthy therapeutic target in NSCLC due to its multiple roles in cancer development and progression. The use of an anti-MET-TKI at any line of treatment is associated with longer OS than previous standard treatment. Limited clinical benefit from anti-PD-(L)1 therapy has been reported for these patients.

Comentários finais

We presented a rare case of synchronous lung adenocarcinomas harboring different mutations, NF1 and MET exon 14 skipping mutation. As they are involved in different mechanisms of carcinogenesis, this leads to a great treatment challenge.

Palavras-chave

Non-small-cell lung cancer; MET; NF1