Circulating tumor cells (Ctc) and kras mutant circulating free Dna (cfdna) detection in peripheral blood as biomarkers in patients diagnosed with exocrine pancreatic cancer.
BACKGROUND
Pancreatic cancer remains one of the most difficult cancers to treat with the poorest prognosis. The key to improving survival rates in this disease is early detection and monitoring of disseminated and residual disease. However, this is hindered due to lack reliable diagnostic and predictive markers which mean that the majority of patients succumb to their condition within a few months.


METHODS
We present a pilot study of the detection circulating free DNA (cfDNA) combined with tumor specific mutation detection by digital PCR as a novel minimally invasive biomarker in pancreatic ductal adenocarcinoma (PDAC). This was compared to the detection of CTC by the CellSearch® system and a novel CTC enrichment strategy based on CD45 positive cell depletion. The aim of the study was to assess tumor specific DNA detection in plasma and CTC detection as prognostic markers in PDAC.


RESULTS
We detected KRAS mutant cfDNA in 26% of patients of all stages and this correlated strongly with Overall Survival (OS), 60 days (95% CI: 19-317) for KRAS mutation positive vs 772 days for KRAS mutation negative (95% CI: 416-1127). Although, the presence of CTC detected by the CellSearch® system did correlate significantly with OS, 88 days (95% CI: 27-206) CTC positive vs 393 days CTC negative (95% CI: 284-501), CTC were detected in only 20% of patients, the majority of which had metastatic disease, whereas KRAS mutant cfDNA was detected in patients with both resectable and advanced disease.


CONCLUSIONS
Tumor specific cfDNA detection and CTC detection are promising markers for the management of patients with PDAC, although there is a need to validate these results in a larger patient cohort and optimize the detection of CTC in PDAC by applying the appropriate markers for their detection.
Medical Oncology Department, Ramón y Cajal University Hospital, Carretera de Colmenar Viejo, KM 9,100, 28034, Madrid, Spain. julie.earl@live.co.uk.
Julie
J
Earl
Medical Oncology Department, Ramón y Cajal University Hospital, Carretera de Colmenar Viejo, KM 9,100, 28034, Madrid, Spain. sandragarcianieto@hotmail.com.
Sandra
S
Garcia-Nieto
Genetic and Molecular Epidemiology Group, Spanish Cancer Research Cancer Center, Madrid, Spain. jcmartinezavila@gmail.com.
Jose Carlos
JC
Martinez-Avila
Pathology Department, Ramón y Cajal University Hospital, Madrid, Spain. jmontans@anatomia.e.telefonica.net.
José
J
Montans
Surgery Department, Ramón y Cajal University Hospital, Madrid, Spain. asanjuanbenito@gmail.com.
Alfonso
A
Sanjuanbenito
Medical Oncology Department, Ramón y Cajal University Hospital, Carretera de Colmenar Viejo, KM 9,100, 28034, Madrid, Spain. mercedes3110@yahoo.es.
Mercedes
M
Rodríguez-Garrote
Surgery Department, Ramón y Cajal University Hospital, Madrid, Spain. edulisa@hotmail.com.
Eduardo
E
Lisa
Surgery Department, Ramón y Cajal University Hospital, Madrid, Spain. mendiaelena@hotmail.com.
Elena
E
Mendía
Surgery Department, Ramón y Cajal University Hospital, Madrid, Spain. eduardo.lobo@salud.madrid.org.
Eduardo
E
Lobo
Genetic and Molecular Epidemiology Group, Spanish Cancer Research Cancer Center, Madrid, Spain. nmalats@cnio.es.
Núria
N
Malats
Medical Oncology Department, Ramón y Cajal University Hospital, Carretera de Colmenar Viejo, KM 9,100, 28034, Madrid, Spain. acarrato@telefonica.net.
Alfredo
A
Carrato
Medical Oncology Department, Ramón y Cajal University Hospital, Carretera de Colmenar Viejo, KM 9,100, 28034, Madrid, Spain. carmenguillenponce@gmail.com.
Carmen
C
Guillen-Ponce
D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D015331:Cohort Studies; D004247:DNA / Q000097:blood* / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology*; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D010865:Pilot Projects; D016283:Proto-Oncogene Proteins p21(ras) / Q000097:blood* / Q000235:genetics; D015996:Survival Rate / Q000639:trends
D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D004247:DNA; D016283:Proto-Oncogene Proteins p21(ras)