SNFGE SNFGE
 
Thématique :
- Cancers autres (hors CCR et CHC)
Originalité :
Intermédiaire
Solidité :
Intermédiaire
Doit faire évoluer notre pratique :
Pas encore
 
 
Nom du veilleur :
Professeur Thomas APARICIO
Coup de coeur :
 
 
Gut
  2019/03  
 
  2019 Mar. pii: gutjnl-2018-317624.  
  doi: 10.1136/gutjnl-2018-317624.  
 
  Immune activation by DNA damage predicts response to chemotherapy and survival in oesophageal adenocarcinoma.  
 
  Turkington RC, Knight LA, Blayney JK, Secrier M, Douglas R, Parkes EE, Sutton EK, Stevenson L, McManus D, Halliday S, McCavigan AM, Logan GE, Walker SM, Steele CJ, Perner J, Bornschein J, MacRae S, Miremadi A, McCarron E, McQuaid S, Arthur K, James JA, Eatock MM, O'Neill R, Noble F, Underwood TJ, Harkin DP, Salto-Tellez M, Fitzgerald RC, Kennedy RD; Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Study Group.  
  https://www.ncbi.nlm.nih.gov/pubmed/30852560  
 
 

Abstract

OBJECTIVE:

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.

DESIGN:

Transcriptional 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).

RESULTS:

A 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).

CONCLUSION:

The 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.

 

 
Question posée
 
Un score immunologique peut-il prédire l’effet de la chimiothérapie néo-adjuvante dans le traitement des adénocarcinomes de l’œsophage ?
 
Question posée
 
Oui.
 
Commentaires

Ce score doit être confirmé et comparé à d’autres. La personnalisation du traitement néo-adjuvant des adénocarcinomes de l’œsophage ou du cardia pour préciser l’intensité de la chimiothérapie et la place de la radiothérapie est un champ de recherche important. 

 
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