Association of Cerebrospinal Fluid Tumor DNA Genotyping With Survival Among Patients With Lung Adenocarcinoma and Central Nervous System Metastases.
JAMA Netw Open
; 3(8): e209077, 2020 08 03.
Article
em En
| MEDLINE
| ID: mdl-32749467
ABSTRACT
Importance Owing to the improvement of systemic therapies for lung cancer, patients live longer, but the incidence of central nervous system (CNS) metastases also increases. Cerebrospinal fluid (CSF) has been proven better than plasma to reveal unique genetic profiling of intracranial metastases. How genetic alterations in CSF are associated with the prognosis of this heterogeneous patient group remains elusive. Objective:
To examine the association of molecular alterations in CSF with the survival of patients with a diagnosis of lung adenocarcinoma and CNS metastases. Design, Setting, andParticipants:
This retrospective cohort analysis of 94 patients with advanced lung adenocarcinoma and CNS metastases was conducted from July 1, 2016, to July 31, 2018. Patients' CSF samples were collected, and next-generation sequencing of CSF circulating tumor DNA was performed. Main Outcome andMeasures:
The main outcome was survival after diagnosis with CNS metastases. Genotyping of CSF circulating tumor DNA was studied to examine its association with the clinical outcomes of patients with CNS metastases.Results:
Of the 94 patients (49 male; mean [SD] age, 53 [1] years) with lung adenocarcinoma and CNS metastases evaluated, 79 harbored an EGFR variant. The most common genes seen in CSF were EGFR (79 [84.0%]), TP53 (57 [60.6%]), MET (23 [24.5%]), CDKN2A (22 [23.4%]), MYC (20 [21.3%]), NTRK1 (19 [20.2%]), and CDK6 (15 [16.0%]). Cluster analysis identified 5 molecular subtypes of CNS metastases. Patients in cluster I had the shortest median survival after diagnosis of CNS metastases compared with each of the other clusters (cluster I, 7.5 months; cluster II, 55.7 months; cluster III, 17.9 months; cluster IV, 27.9 months; cluster V, 21.0 months) and significantly increased risk of death compared with patients in the other clusters (cluster II hazard ratio [HR], 4.95; 95% CI, 1.50-16.41; P = .009; cluster III HR, 4.75; 95% CI, 1.49-15.12; P = .008; cluster IV HR, 6.38; 95% CI, 1.76-23.09; P = .005; cluster V HR, 5.42; 95% CI, 1.63-17.98; P = .006). The genetic profiles of cluster I were characterized by a high detection rate of CDK4 (9 of 9 [100%]), TP53 (8 of 9 [88.9%]), MET (7 of 9 [77.8%]), and CDKN2A (7 of 9 [77.8%]). For those with EGFR variants, coalterations with CDK4 (HR, 2.02; 95% CI, 1.03-3.96; P = .04), CDK6 (HR, 2.52; 95% CI, 1.32-4.83; P = .005), and MYC (HR, 2.24; 95% CI, 1.21-4.15; P = .01) were associated with poor outcomes. Conclusions and Relevance Patients with a diagnosis of lung adenocarcinoma and CNS metastases experienced heterogeneous survival outcomes based on genetic profiling in CSF. These data suggest that CSF might facilitate risk stratifying CNS metastases into appropriate outcomes and provide reference for further clinical study.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias do Sistema Nervoso Central
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DNA Tumoral Circulante
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Adenocarcinoma de Pulmão
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Neoplasias Pulmonares
Tipo de estudo:
Observational_studies
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Risk_factors_studies
Limite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article