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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?

SUBMITTER: Lohinai Z

PROVIDER: S-EPMC5209707 | biostudies-other | 2017 Jan

REPOSITORIES: biostudies-other

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

Lohinai Zoltan Z Klikovits Thomas T Moldvay Judit J Ostoros Gyula G Raso Erzsebet E Timar Jozsef J Fabian Katalin K Kovalszky Ilona I Kenessey István I Aigner Clemens C Renyi-Vamos Ferenc F Klepetko Walter W Dome Balazs B Hegedus Balazs B

Scientific reports 20170104

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%), ...[more]

PMID: 28051122

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Project description:ObjectivesThere is no molecular biomarker available in the clinical practice to assess the prognosis of advanced pancreatic carcinoma. This multicenter prospective study aimed to investigate the role of KRAS mutation subtypes within the primary tumor to determine the prognosis of advanced pancreatic cancer.MethodsThe exon-2 KRAS mutation status was tested on endoscopic ultrasound-guided fine-needle aspiration biopsy material (primary tumor; restriction fragment-length polymorphism plus sequencing and TaqMan allelic discrimination) of patients with proven locally advanced and/or metastatic pancreatic ductal carcinoma. We used the Kaplan-Meier method, log-rank test, and Cox's model to evaluate the impact of KRAS status on the overall survival (OS), adjusting for age, stage of disease, clinical performance status, CA 19-9 levels, and treatment.ResultsA total of 219 patients (men: 116; mean age: 67±9.4 years) were included: 147 harbored a codon-12 KRAS mutation (G12D: 73; G12V: 53; G12R: 21) and 72 had a wild-type KRAS. There was no difference in the OS between patients with a mutant KRAS (8 months; 95% confidence interval (95% CI): 8.7-12.3) and the wild-type (9 months; 95% CI: 8.7-12.8; hazard ratio (HR): 1.03; P=0.82). However, the patients with a G12D mutation had a significantly shorter OS (6 months; 95% CI: 6.4-9.7) compared with the other patients (OS: 9 months; 95% CI: 10-13; HR: 1.47; P=0.003; i.e., wild type: 9 months, G12V: 9 months, G12R: 14 months). Similar results were observed in the subgroup of 162 patients who received chemotherapy (HR: 1.66; P=0.0013; G12D (n=49): 8 months, wild type (n=56): 10 months, G12V (n=38): 10 months, G12R (n=19): 14 months). Multivariate analyses identified KRAS G12D as an independent predictor for worse prognosis within the entire series (HR: 1.44; P=0.01) and in the subgroup of patients that received chemotherapy (HR: 1.84; P=0.02).ConclusionsThe KRAS G12D mutation subtype is an independent prognostic marker for advanced pancreatic ductal carcinoma. Codon and amino-acid-specific mutations of KRAS should be considered when evaluating the prognoses as well as in trials testing drugs that target RAS and downstream RAS pathways.

Project description:BackgroundFor adolescents and young adults (AYAs, aged 15-39 years) with cancer, metastatic disease at diagnosis is the strongest predictor of mortality, but its associations with age and sociodemographic factors are largely unexplored.MethodsUsing Surveillance, Epidemiology, and End Results Program data from 2000 to 2016, we collected incident cases of poor-prognosis metastatic cancer (5-year survival < 50%) and compared the proportion, incidence, time trends, and incidence rate ratios for race and ethnicity, sex, and socioeconomic status among AYAs, middle-aged adults (aged 40-64 years) and older adults (aged 65-79 years).ResultsFrom 2000 to 2016, a total of 17 210 incident cases of poor-prognosis metastatic cancer were diagnosed in AYAs, 121 274 in middle-aged adults, and 364 228 in older adults. Compared with older patients, the proportion of AYAs having metastatic disease was equivalent or substantially lower in nearly every site except stomach and breast cancers, which were statistically significantly higher for AYAs compared with middle-aged and older adults (stomach: 57.3% vs 46.4% and 39.5%; breast: 6.6% vs 4.4% and 5.6%, respectively; 2-sided P < .001 for all comparisons). Incidence rates rose significantly faster among AYAs for breast, stomach, and kidney cancers and among AYAs and middle-aged adults for colorectal cancer. Markedly higher incidence rate ratios were noted for AYA racial and ethnic minorities with breast, stomach, and especially kidney cancer, where only non-Hispanic Black AYAs were at considerably higher risk. For most sites, incidence rate ratios were higher among male patients and individuals of low socioeconomic status across age groups.ConclusionsFor most cancers, AYAs are not more likely to present with metastases than middle-aged and older adults. Further investigation is warranted for the disproportionate rise in incidence of metastatic breast, stomach, and kidney cancer among AYAs and their excess burden among AYA racial and ethnic minorities. The rising incidence of colorectal cancer among AYAs and middle-aged adults remains an additional concern.

Dataset Information

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

Publications

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

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