Pancreatic cancer: Are "liquid biopsies" ready for prime-time?

Table 1 Studies reporting detection of circulating tumour cells in patients with pancreatic cancer

Study	CTC platform	Markers	Stage of disease	Time of sampling	Number of patients, n	Cut-off for positivity per 7. 5 mL blood	CTCs detected, n
Zhang et al[16] 2014	Immunocy-togenetics	CK, CD45, DAPI, CEP8	All stages	Pre-operative	22	4	16/22 (72.7%)
Rhim et al[17] 2014	Micro-fluidic "GEM" Chip	DAPI, CD45, CK, PDX-1	All stages	Diagnosis	11	≥ 1	8/11 (73%)
Khoja et al[12] 2011	CellSearch and ISET	EpCAM, CK, vimentin, E-cadherin	All stages	Diagnosis or at time of diagnosis of progressive disease > 6 wk from therapy	53	≥ 1	21/53 (40%) using CellSearch
							24/27 (93%) using ISET
Nagrath et al[18] 2013	CTC-Chip	Cks	Metastatic	Not stated	15	37.5 (5/mL)	15/15 (100%)
Allard et al[15] 2004	CellSearch	CK8, CK18, CK19	Metastatic	Not stated	16	≥ 1	6/16 ((38%)
Gall et al[19] 2013	CellSearch	EpCam, EGFR	Locally advanced	Pre-treatment	75	≥ 1	4/75 (5%)
Ren et al[20] 2011	Immuno-cyto-chemistry	CA 19-9, CK8, CK18	Locally advanced and metastatic	Pre- and post- treatment	41	≥ 1	33/41 (80.5%) pre-treatment and 12/41 (29.3%) post-treatment

CTC: Circulating tumour cell.

Table 2 Studies reporting detection of circulating tumour DNA in patients with pancreatic cancer

Study	CtDNA platform	Markers	Stage of disease	Time of sampling	Number of patients, n	Markers detected, n
Zhou et al[32] 2011	Nested RT-PCR	H-tert, C-MET, CK20, CEA mRNAs	All stages	Pre-treatment	25	H-TERT 25/25 (100%)
						CMET 20/25(80%), CK20 21/25 (84%), CEA 20/25 (80%)
de Albuquerque et al[22] 2012	Immunomagnetic RT-PCR	KRT19, MUC1, EpCAM, CEACAM5, BIRC5	Stage III and IV	Pre-treatment	34	16/34 (47%)
Chausovsky et al[33] 1999	RT-PCR	CK20	Metastatic	Not stated	28	22/28 (79%)
Sausen et al[28] 2015	Digital PCR	KRAS	Localised	Pre-treatment	51	22/51 (43%)
Earl et al[27] 2015	Digital PCR	KRAS	All stages	Pre-treatment (NB 7 patients had received chemotherapy)	31	8/31 (26%)
Sergeant et al[31] 2011	RT-PCR	EpCAM	Stage I,II and 4	Pre and post treatment	40	10/40 (25%) preoperatively,
						10/35(28.6%) D1, 9/39 (23.1%) at D7, 8/34 (23.5%) at 6 wk
Bettegowda et al[26] 2014	Digital PCR	KRAS, NRAS, PIK3CA, BRAF	Localised and metastatic	Not stated	155	48% of those with localised and > 80% metastatic disease
Zill et al[30] 2015	NGS	KRAS, TP53, APC, SMAD4, FBXW7	Localised and metastatic	Post-treatment	17	17/17 (100%)
Kinugasa et al[29] 2015	Digital PCR	KRAS	All stages	Pre-treatment	75	47/75 (62%)

CtDNA: Circulating tumour DNA; RT-PCR: Reverse transcription polymerase chain reaction.