Performance and cost efficiency of KRAS mutation testing for metastatic colorectal cancer in routine diagnosis: the MOKAECM study, a nationwide experience.
OBJECTIVE
Rapid advances in the understanding of cancer biology have transformed drug development thus leading to the approval of targeted therapies and to the development of molecular tests to select patients that will respond to treatments. KRAS status has emerged as a negative predictor of clinical benefit from anti-EGFR antibodies in colorectal cancer, and anti-EGFR antibodies use was limited to KRAS wild type tumors. In order to ensure wide access to tumor molecular profiling, the French National Cancer Institute (INCa) has set up a national network of 28 regional molecular genetics centers. Concurrently, a nationwide external quality assessment for KRAS testing (MOKAECM) was granted to analyze reproducibility and costs.


METHODS
96 cell-line DNAs and 24 DNA samples from paraffin embedded tumor tissues were sent to 40 French laboratories. A total of 5448 KRAS results were collected and analyzed and a micro-costing study was performed on sites for 5 common methods by an independent team of health economists.


RESULTS
This work provided a baseline picture of the accuracy and reliability of KRAS analysis in routine testing conditions at a nationwide level. Inter-laboratory Kappa values were >0.8 for KRAS results despite differences detection methods and the use of in-house technologies. Specificity was excellent with only one false positive in 1128 FFPE data, and sensitivity was higher for targeted techniques as compared to Sanger sequencing based methods that were dependent upon local expertise. Estimated reagent costs per patient ranged from €5.5 to €19.0.


CONCLUSIONS
The INCa has set-up a network of public laboratories dedicated to molecular oncology tests. Our results showed almost perfect agreements in KRAS testing at a nationwide level despite different testing methods ensuring a cost-effective equal access to personalized colorectal cancer treatment.
UMR-S775, INSERM, Paris, France.
Hélène
H
Blons
Etienne
E
Rouleau
Nathanaël
N
Charrier
Gilles
G
Chatellier
Jean-François
JF
Côté
Jean-Christophe
JC
Pages
Florence
F
de Fraipont
Jean-Christophe
JC
Boyer
Jean Philippe
JP
Merlio
Alain
A
Morel
Marie-Claude
MC
Gorisse
Patricia
P
de Cremoux
Karen
K
Leroy
Gérard
G
Milano
L'houcine
L
Ouafik
Jean-Louis
JL
Merlin
Delphine
D
Le Corre
Pascaline
P
Aucouturier
Jean-Christophe
JC
Sabourin
Frédérique
F
Nowak
Thierry
T
Frebourg
Jean-François
JF
Emile
Isabelle
I
Durand-Zaleski
Pierre
P
Laurent-Puig
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001706:Biopsy; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000191:economics* / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D005404:Fixatives; D005602:France; D005820:Genetic Testing / Q000191:economics* / Q000379:methods; D006801:Humans; D009362:Neoplasm Metastasis; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000191:economics* / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA / Q000191:economics / Q000379:methods; D016610:Tissue Embedding; D018631:ras Proteins / Q000032:analysis / Q000191:economics* / Q000235:genetics*
D000911:Antibodies, Monoclonal; D005404:Fixatives; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins