KRAS-mutation incidence and prognostic value are metastatic site-specific in lung adenocarcinoma: poor prognosis in patients with KRAS mutation and bone metastasis

Abstract

Current guidelines lack comprehensive information on the metastatic site-specific role of KRAS mutation in lung adenocarcinoma (LADC). We investigated the effect of KRAS mutation on overall survival (OS) in this setting. In our retrospective study, 500 consecutive Caucasian metastatic LADC patients with known KRAS mutational status were analyzed after excluding 32 patients with EGFR mutations. KRAS mutation incidence was 28.6%. The most frequent metastatic sites were lung (45.6%), bone (26.2%), adrenal gland (17.4%), brain (16.8%), pleura (15.6%) and liver (11%). Patients with intrapulmonary metastasis had significantly increased KRAS mutation frequency compared to those with extrapulmonary metastases (35% vs 26.5%, p = 0.0125). In contrast, pleural dissemination and liver involvement were associated with significantly decreased KRAS mutation incidence (vs all other metastatic sites; 17% (p < 0.001) and 16% (p = 0.02) vs 33%, respectively). Strikingly, we found a significant prognostic effect of KRAS status only in the bone metastatic subcohort (KRAS-wild-type vs KRAS-mutant; median OS 9.7 v 3.7 months; HR, 0.49; 95% CI, 0.31 to 0.79; p = 0.003). Our study suggests that KRAS mutation frequency in LADC patients shows a metastatic site dependent variation and, moreover, that the presence of KRAS mutation is associated with significantly worse outcome in bone metastatic cases.

Molecular Pathology of Lung Cancer

“…Kirsten sıçan sarkomaviral onkogen (KRAS) mutasyonu akciğer adenokarsinomlarında izlenen en sık (%20-30) onkojenik değişikliklerden biridir (33). KRAS mutasyonu PCR veya sekanslama yöntemleriyle tespit edilebilir.…”

Frequency and outcomes of brain metastases in patients with HER2‐mutant lung cancers

“…For context with other patients with NSCLC, rates of brain metastasis in HER2 ‐mutant lung cancers were compared with frequencies in the more readily studied epidermal growth factor receptor ( EGFR )–mutant and KRAS ‐mutant lung adenocarcinomas. KRAS ‐mutant lung cancers compose 29% to 33% of lung adenocarcinomas, and 17% to 55% of these patients develop brain metastases . EGFR ‐mutant lung cancers compose 11% to 25% of lung adenocarcinomas, with up to 60% of these patients developing brain metastases or leptomeningeal disease during their illness .…”

Possible application of circulating free tumor DNA in non-small cell lung cancer patients

“…KRAS mutations indicate a poor outcome of the patients and currently there is not any efficient targeted therapy for this disease (48).…”