KRAS p.G12C mutation occurs in 1% of EGFR-mutated advanced non-small-cell lung cancer patients progressing on a first-line treatment with a tyrosine kinase inhibitor.

BACKGROUND: KRAS is mutated in ∼30% of non-small-cell lung cancer (NSCLC) but it has also been identified as one of the mechanisms underlying resistance to tyrosine kinase inhibitors (TKIs) in EGFR-positive NSCLC patients. Novel KRAS inhibitors targeting KRAS p.G12C mutation have been developed recently with promising results. The proportion of EGFR-positive NSCLC tumours harbouring the KRAS p.G12C mutation upon disease progression is completely unexplored. MATERIALS AND METHODS: Plasma samples from 512 EGFR-positive advanced NSCLC patients progressing on a first first-line treatment with a TKI were collected. The presence of KRAS p.G12C mutation was assessed by digital PCR. RESULTS: Overall, KRAS p.G12C mutation was detected in 1.17% of the samples (n = 6). In two of these cases, we could confirm that the KRAS p.G12C mutation was not present in the pre-treatment plasma samples, supporting its role as an acquired resistance mutation. According to our data, KRASG12C patients showed similar clinicopathological characteristics to those of the rest of the study cohort and no statistically significant associations between any clinical features and the presence of the mutation were found. However, two out of six KRASG12C tumours harboured less common EGFR driver mutations (p.G719X/p.L861Q). All KRASG12C patients tested negative for the presence of p.T790M resistance mutation. CONCLUSIONS: The KRAS p.G12C mutation is detected in 1% of EGFR-positive NSCLC patients who progress on a first line with a TKI. All KRASG12C patients were negative for the presence of the p.T790M mutation and they did not show any distinctive clinical feature.

[Bilateral neurotrophic keratitis secondary to encephalic trunk metastasis]. / Queratopatía neurotrófica bilateral secundaria a metástasis en tronco del encéfalo.

CASE REPORT: We report the case of a 69-year-old man with a lung carcinoma history. The patient showed signs of conjuntival hyperemia, painless bilateral corneal edema, persistent epitelial defects and reported to have decreasing visual acuity for a week. The clinical examination revealed a bilateral neurotrophyc keratitis with both a decreased frequency of blinking and a bilateral atrophy mandibular muscles. Local ocular patology was excluded. Systemic exploration showed a meningeal neoplasic infiltration and metastasis on the initial trigeminal nerve stretch. In our knowledge, this is the first case reported in the literature. DISCUSSION: Ophthalmic signs should be considered in the diagnosis of systemic pathology.

Queratopatía neurotrófica bilateral secundaria a metástasis en tronco del encéfalo / Bilateral neurotrophic keratitis secondary to encephalic trunk metastasis

Caso clínico: Presentamos un paciente de 69 años de edad con antecedentes de neoplasia pulmonar que presentaba hiperemia conjuntival, infiltración corneal bilateral no dolorosa y disminución de la agudeza visual de 1 semana de evolución. La exploración clínica reveló una queratopatía neurotrófica bilateral con disminución en la frecuencia del parpadeo y atrofia masetera bilateral. Tras descartarse patología ocular local, las pruebas complementarias objetivaron carcinomatosis meníngea con metástasis de los trayectos cisternales de los V pares craneales. No encontramos referencias de un caso similar en la bibliografía. Discusión: Debemos considerar la clínica oftalmológica en el diagnóstico de las enfermedades sistémicas no manifiestas (AU)