SNFGE SNFGE
 
Thématique :
- Cancers autres (hors CCR et CHC)
Originalité :
Très original
Solidité :
Intermédiaire
Doit faire évoluer notre pratique :
Dans certains cas
 
 
Nom du veilleur :
Professeur Thomas APARICIO
Coup de coeur :
 
 
Gut
  2018/02  
 
  2018 Feb. pii: gutjnl-2017-315852.  
  doi: 10.1136/gutjnl-2017-315852  
 
  Serial circulating tumour DNA analysis during multimodality treatment of locally advanced rectal cancer: a prospective biomarker study.  
 
  Tie J, Cohen JD, Wang Y, Li L, Christie M, Simons K, Elsaleh H, Kosmider S, Wong R, Yip D, Lee M, Tran B, Rangiah D, Burge M, Goldstein D, Singh M, Skinner I, Faragher I, Croxford M, Bampton C, Haydon A, Jones IT, S Karapetis C, Price T, Schaefer MJ, Ptak J, Dobbyn L, Silliman N, Kinde I, Tomasetti C, Papadopoulos N, Kinzler K, Volgestein B, Gibbs P  
  https://www.ncbi.nlm.nih.gov/pubmed/29420226  
 
 

Abstract

OBJECTIVE:

For patients with locally advanced rectal cancer (LARC), adjuvant chemotherapy selection following surgery remains a major clinical dilemma. Here, we investigated the ability of circulating tumour DNA (ctDNA) to improve risk stratification in patients with LARC.

DESIGN:

We enrolled patients with LARC (T3/T4 and/or N+) planned for neoadjuvant chemoradiotherapy. Plasma samples were collected pretreatment, postchemoradiotherapy and 4-10 weeks after surgery. Somatic mutations in individual patient's tumour were identified via massively parallel sequencing of 15 genes commonly mutated in colorectal cancer. We then designed personalised assays to quantify ctDNA in plasma samples. Patients received adjuvant therapy at clinician discretion, blinded to the ctDNA results.

RESULTS:

We analysed 462 serial plasma samples from 159 patients. ctDNA was detectable in 77%, 8.3% and 12% of pretreatment, postchemoradiotherapy and postsurgery plasma samples. Significantly worse recurrence-free survival was seen if ctDNA was detectable after chemoradiotherapy (HR 6.6; P<0.001) or after surgery (HR 13.0; P<0.001). The estimated 3-year recurrence-free survival was 33% for the postoperative ctDNA-positive patients and 87% for the postoperative ctDNA-negative patients. Postoperative ctDNA detection was predictive of recurrence irrespective of adjuvant chemotherapy use (chemotherapy: HR 10.0; P<0.001; without chemotherapy: HR 22.0; P<0.001). Postoperative ctDNA status remained an independent predictor of recurrence-free survival after adjusting for known clinicopathological risk factors (HR 6.0; P<0.001).

CONCLUSION:

Postoperative ctDNA analysis stratifies patients with LARC into subsets that are either at very high or at low risk of recurrence, independent of conventional clinicopathological risk factors. ctDNA analysis could potentially be used to guide patient selection for adjuvant chemotherapy.

 

 
Question posée
 
La détection d’ADN tumoral circulant post opératoire peut-il prédire la récidive ?
 
Question posée
 
Oui.
 
Commentaires

La question de la chimiothérapie adjuvante après résection d’un adénocarcinome rectal n’est pas résolue. La fluctuation de l’ADNt circulant a déjà été montrée associé à la réponse tumorale des formes métastatique. Cette étude montre qu’il peut également être utilisé comme prédicteur de récidive dans les cancers localisés. Cependant la méthode utilisée implique de rechercher les mutations existantes au niveau de la tumeur primitive. Le passage en routine d’une telle méthode ne sera pas simple.  

 
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