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Next‐generation sequencing and clinical outcomes of patients with lung adenocarcinoma treated with stereotactic body radiotherapy
Cancer, 2017-10, Vol.123 (19), p.3681-3690
Cassidy, Richard J.
Zhang, Xinyan
Patel, Pretesh R.
Shelton, Joseph W.
Escott, Chase E.
Sica, Gabriel L.
Rossi, Michael R.
Hill, Charles E.
Steuer, Conor E.
Pillai, Rathi N.
Ramalingam, Suresh S.
Owonikoko, Taofeek K.
Behera, Madhusmita
Force, Seth D.
Fernandez, Felix G.
Curran, Walter J.
Higgins, Kristin A.
2017
Volltextzugriff (PDF)
Details
Autor(en) / Beteiligte
Cassidy, Richard J.
Zhang, Xinyan
Patel, Pretesh R.
Shelton, Joseph W.
Escott, Chase E.
Sica, Gabriel L.
Rossi, Michael R.
Hill, Charles E.
Steuer, Conor E.
Pillai, Rathi N.
Ramalingam, Suresh S.
Owonikoko, Taofeek K.
Behera, Madhusmita
Force, Seth D.
Fernandez, Felix G.
Curran, Walter J.
Higgins, Kristin A.
Titel
Next‐generation sequencing and clinical outcomes of patients with lung adenocarcinoma treated with stereotactic body radiotherapy
Ist Teil von
Cancer, 2017-10, Vol.123 (19), p.3681-3690
Ort / Verlag
United States: Wiley Subscription Services, Inc
Erscheinungsjahr
2017
Quelle
Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
Beschreibungen/Notizen
BACKGROUND Genetic aberrations are well characterized in lung adenocarcinomas (LACs) and clinical outcomes have been influenced by targeted therapies in the advanced setting. Stereotactic body radiotherapy (SBRT) is the standard‐of‐care therapy for patients with nonoperable, early‐stage LAC, but to the authors' knowledge, no information is available regarding the impact of genomic changes in these patients. The current study sought to determine the frequency and clinical impact of genetic aberrations in this population. METHODS Under an Institutional Review Board‐approved protocol, the records of 242 consecutive patients with early‐stage lung cancers were reviewed; inclusion criteria included LAC histology with an adequate tumor sample for the successful use of next‐generation sequencing and fluorescence in situ hybridization testing. Univariate analysis was performed to identify factors associated with clinical outcomes. RESULTS LAC samples from 98 of the 242 patients were reviewed (40.5%), of whom 45 patients (46.0%) had genetic testing. The following mutations were noted: KRAS in 20.0% of samples, BRAF in 2.2% of samples, SMAD family member 4 (SMAD4) in 4.4% of samples, epidermal growth factor receptor (EGFR) in 15.6% of samples, STK1 in 2.2% of samples, tumor protein 53 (TP53) in 15.6% of samples, and phosphatase and tensin homolog (PTEN) in 2.2% of samples. The following gene rearrangements were observed: anaplastic lymphoma kinase (ALK) in 8.9% of samples, RET in 2.2% of samples, and MET amplification in 17.8% of samples. The median total delivered SBRT dose was 50 grays (range, 48‐60 grays) over a median of 5 fractions (range, 3‐8 fractions). The KRAS mutation was associated with worse local control (odds ratio [OR], 3.64; P<.05). MET amplification was associated with worse regional (OR, 4.64; P<.05) and distant (OR, 3.73; P<.05) disease control. CONCLUSIONS To the authors' knowledge, the current series is the first to quantify genetic mutations and their association with clinical outcomes in patients with early‐stage LAC treated with SBRT. KRAS mutations were associated with worse local control and MET amplification was associated with worse regional and distant disease control, findings that need to be validated in a prospective setting. Cancer 2017;123:3681–3690. © 2017 American Cancer Society To the authors' knowledge, no data exist regarding the prevalence of next‐generation sequencing‐detected mutations in patients with early‐stage lung adenocarcinomas who are treated with stereotactic body radiotherapy. Herein, the authors report that the incidence of mutations and gene amplifications in patients with early‐stage lung adenocarcinomas who are treated with stereotactic body radiotherapy is congruent with the advanced disease setting and that patients with KRAS‐mutated tumors appear to have poorer local control and those with MET‐amplified tumors have poorer regional and distant control.
Sprache
Englisch
Identifikatoren
ISSN: 0008-543X
eISSN: 1097-0142
DOI: 10.1002/cncr.30794
Titel-ID: cdi_proquest_miscellaneous_1909234106
Format
–
Schlagworte
Aberration
,
Adenocarcinoma
,
Adenocarcinoma - genetics
,
Adenocarcinoma - mortality
,
Adenocarcinoma - pathology
,
Adenocarcinoma - radiotherapy
,
Adenocarcinoma of Lung
,
Adult
,
Aged
,
Aged, 80 and over
,
Amplification
,
Analysis of Variance
,
Anaplastic Lymphoma Kinase
,
Cancer
,
Chromosome Aberrations
,
Clinical outcomes
,
Disease control
,
Epidermal growth factor
,
Epidermal growth factor receptors
,
Female
,
Fluorescence
,
Fluorescence in situ hybridization
,
fms-Like Tyrosine Kinase 3 - genetics
,
Gene Rearrangement
,
Genes, erbB-1
,
Genes, p53
,
Genes, ras
,
Genetic screening
,
High-Throughput Nucleotide Sequencing - methods
,
Histology
,
Homology
,
Humans
,
In Situ Hybridization, Fluorescence
,
K-Ras protein
,
lung adenocarcinomas
,
Lung cancer
,
lung mutations
,
Lung Neoplasms - genetics
,
Lung Neoplasms - mortality
,
Lung Neoplasms - pathology
,
Lung Neoplasms - radiotherapy
,
Lungs
,
Lymphoma
,
Male
,
Middle Aged
,
Molecular Targeted Therapy
,
Mutation
,
Neoplasm Recurrence, Local
,
next‐generation sequencing
,
Oncology
,
p53 Protein
,
Patients
,
Population genetics
,
Protein-tyrosine kinase
,
Proto-Oncogene Proteins B-raf - genetics
,
Proto-Oncogene Proteins c-met - genetics
,
Proto-Oncogene Proteins c-ret - genetics
,
PTEN Phosphohydrolase - genetics
,
PTEN protein
,
Radiation therapy
,
Radiosurgery
,
Receptor Protein-Tyrosine Kinases - genetics
,
Sequences
,
Smad protein
,
Smad4 protein
,
Smad4 Protein - genetics
,
stereotactic body radiotherapy
,
targeted therapy
,
Tensin
,
Tumors
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