Sökning: WFRF:(Lagergren M.) > (2015-2019) > Immune activation b...
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000 | 06102naa a2201477 4500 | |
001 | oai:prod.swepub.kib.ki.se:142430259 | |
003 | SwePub | |
008 | 240818s2019 | |||||||||||000 ||eng| | |
024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1424302592 URI |
024 | 7 | a https://doi.org/10.1136/gutjnl-2018-3176242 DOI |
040 | a (SwePub)ki | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Turkington, RC4 aut |
245 | 1 0 | a Immune activation by DNA damage predicts response to chemotherapy and survival in oesophageal adenocarcinoma |
264 | c 2019-03-09 | |
264 | 1 | b BMJ,c 2019 |
520 | a Current strategies to guide selection of neoadjuvant therapy in oesophageal adenocarcinoma (OAC) are inadequate. We assessed the ability of a DNA damage immune response (DDIR) assay to predict response following neoadjuvant chemotherapy in OAC.DesignTranscriptional profiling of 273 formalin-fixed paraffin-embedded prechemotherapy endoscopic OAC biopsies was performed. All patients were treated with platinum-based neoadjuvant chemotherapy and resection between 2003 and 2014 at four centres in the Oesophageal Cancer Clinical and Molecular Stratification consortium. CD8 and programmed death ligand 1 (PD-L1) immunohistochemical staining was assessed in matched resection specimens from 126 cases. Kaplan-Meier and Cox proportional hazards regression analysis were applied according to DDIR status for recurrence-free survival (RFS) and overall survival (OS).ResultsA total of 66 OAC samples (24%) were DDIR positive with the remaining 207 samples (76%) being DDIR negative. DDIR assay positivity was associated with improved RFS (HR: 0.61; 95% CI 0.38 to 0.98; p=0.042) and OS (HR: 0.52; 95% CI 0.31 to 0.88; p=0.015) following multivariate analysis. DDIR-positive patients had a higher pathological response rate (p=0.033), lower nodal burden (p=0.026) and reduced circumferential margin involvement (p=0.007). No difference in OS was observed according to DDIR status in an independent surgery-alone dataset.DDIR-positive OAC tumours were also associated with the presence of CD8+ lymphocytes (intratumoural: p<0.001; stromal: p=0.026) as well as PD-L1 expression (intratumoural: p=0.047; stromal: p=0.025).ConclusionThe DDIR assay is strongly predictive of benefit from DNA-damaging neoadjuvant chemotherapy followed by surgical resection and is associated with a proinflammatory microenvironment in OAC. | |
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700 | 1 | a Lagergren, Ju Karolinska Institutet4 aut |
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710 | 2 | a Karolinska Institutet4 org |
773 | 0 | t Gutd : BMJg 68:11, s. 1918-1927q 68:11<1918-1927x 1468-3288x 0017-5749 |
856 | 4 | u https://gut.bmj.com/content/gutjnl/68/11/1918.full.pdf |
856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:142430259 |
856 | 4 8 | u https://doi.org/10.1136/gutjnl-2018-317624 |
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