Reduced genomic tumor heterogeneity after neoadjuvant chemotherapy is related to favorable outcome in patients with esophageal adenocarcinoma.
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Date
2016-07ICR Author
Author
Obulkasim, A
Ylstra, B
van Essen, HF
Benner, C
Stenning, S
Langley, R
Allum, W
Cunningham, D
Inam, I
Hewitt, LC
West, NP
Meijer, GA
van de Wiel, MA
Grabsch, HI
Type
Journal Article
Metadata
Show full item recordAbstract
Neoadjuvant chemo(radio)therapy followed by surgery is the standard of care for patients with locally advanced resectable esophageal adenocarcinoma (EAC). There is increasing evidence that drug resistance might be related to genomic heterogeneity. We investigated whether genomic tumor heterogeneity is different after cytotoxic chemotherapy and is associated with EAC patient survival. We used arrayCGH and a quantitative assessment of the whole genome DNA copy number aberration patterns ('DNA copy number entropy') to establish the level of genomic tumor heterogeneity in 80 EAC treated with neoadjuvant chemotherapy followed by surgery (CS group) or surgery alone (S group). The association between DNA copy number entropy, clinicopathological variables and survival was investigated.DNA copy number entropy was reduced after chemotherapy, even if there was no morphological evidence of response to therapy (p<0.001). Low DNA copy number entropy was associated with improved survival in the CS group (p=0.011) but not in the S group (p=0.396).Our results suggest that cytotoxic chemotherapy reduces DNA copy number entropy, which might be a more sensitive tumor response marker than changes in the morphological tumor phenotype. The use of DNA copy number entropy in clinical practice will require validation of our results in a prospective study.
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Subject
Humans
Adenocarcinoma
Esophageal Neoplasms
Antineoplastic Combined Chemotherapy Protocols
Treatment Outcome
Chemotherapy, Adjuvant
Neoadjuvant Therapy
Survival Analysis
Retrospective Studies
Pilot Projects
Gene Expression Profiling
Genetic Heterogeneity
Adult
Aged
Aged, 80 and over
Middle Aged
Female
Male
DNA Copy Number Variations
Research team
Medicine (RMH Smith Cunningham)
Language
eng
Date accepted
2016-04-29
License start date
2016-07
Citation
Oncotarget, 2016, 7 (28), pp. 44084 - 44095