Table 1.
Previous CTC studies focusing on pancreatic cancer
| Enrichment strategy | Refs | N | Stage | Detection strategy | Detection rate | Enumeration | ||
|---|---|---|---|---|---|---|---|---|
|
IM CellSearch® |
EpCAM | Dotan et al. (2016) | 48 | IV | IF | DAPI+/CD45−/panCK+, MUC‐1+ | 48% (23/48) (≥ 1 CTC): 13% (6/48) (≥ 2 CTCs); 8% (3/37) (≥ 2 CTCs) at first evaluation after Tx | NA |
| Piegeler et al. (2016) | 8 |
IB (n = 1) IIB (n = 1) III (n = 2) IV (n = 4) |
IF | DAPI+/CD45−/CK+ | 87.5% (7/8): 100% (1/1) in Stage IB; 100% (1/1) in Stage IIB; 100% (2/2) in Stage III; 75% (3/4) in Stage IV | Median 4.5 CTCs/7.5 mL, range 0–83 CTCs/7.5 mL | ||
| Bissolati et al. (2015) | 20 | R | IF | DAPI+/CD45−/panCK+ |
20% (4/20) in PB 40% (8/20) in PV |
NA | ||
| Catenacci et al. (2015) | 14 | IIB‐IV | IF | DAPI+/CD45−/EpCAM+ |
21.4% (3/14) in PB 100% (14/14) in PV |
(1) In PB, mean 0.7 CTCs/7.5 mL, median 0 CTCs/7.5 mL, range 0–7 CTCs/7.5 mL. (2) In PV, mean 125.64 CTCs/7.5 mL, median 68.5 CTCs/7.5 mL, range 1–516 CTCs/7.5 mL | ||
| Earl et al. (2015) | 35 |
R (n = 10) LA (n = 11) M (n = 14) |
IF | DAPI+/CD45−/CK+ |
20% (7/35) in total 10% (1/10) in R 42.8% (6/14) in M |
Mean 0.77 CTCs/7.5 mL in total, mean 0.1 CTCs/7.5 mL in R, mean 1.9 CTCs/7.5 mL in M | ||
| Bidard et al. (2013) | 79 | III | IF | CD45−/CK+, EGFR |
5% (4/75) at baseline 9% (5/56) at first evaluation 11% (9/79) in total 50% (2/4) in Stage IV (control) |
1–15 CTCs/7.5 mL | ||
| Kurihara et al. (2008) | 26a |
II (n = 1) III (n = 1) IVA (n = 10) IVB (n = 14) |
IF | DAPI+/CD45−/panCK+ |
42% (11/26) in total 45.8% (11/24) in Stage IV |
Mean 16.9 CTCs/7.5 mL, range 1–105 CTCs/7.5 mL | ||
| Allard et al. (2004) | 16a | IV | IF | DAPI+/CD45−/panCK+ | 19% (4/21) (≥ 2 CTCs) of the samples | Mean 2 ± 6 CTCs/7.5 mL, median 3.5 CTCs/7.5 mL | ||
|
IM CellCollector® |
EpCAM | El‐Heliebi et al. (2018) | 15 |
I (n = 7) II‐III (n = 6) NA (n = 2) |
RCA, IF | KRAS, DAPI+/CD45−/CK18 or PanCK± | 47% (7/15) KRAS mut 40% (6/15) |
Range 1–3 CTCs/patient, KRAS mut 1–8 RCPs/CTC, KRAS wt 1–2 RCPs/CTC |
|
IM MACS |
EpCAM | Effenberger et al. (2018) | 69 | I (n = 2) II (n = 30) III (n = 10) IV (n = 27) |
IF | DAPI+/CD45−/CK+ | 33.3% (23/69) | Range 1–19 CTCs/7.5 mL |
| Zhou et al. (2011) | 25a |
I‐II (n = 5) III (n = 8) IV (n = 12) |
RT–PCR | h‐TERT, CK20, CEA, C‐MET | 100% (25/25) | NA | ||
|
IM Dynabeads® |
MUC1 EpCAM |
de Albuquerque et al. (2012) | 34 | II‐IV | RT–PCR | KRT19, MUC1, EPCAM, CEACAM5, BIRC5 | 47.1% (16/34): 20.6% for KRT19 and MUC1; 23.5% for EPCAM; 2.9% for CEACAM5; 17.6% for BIRC5 | NA |
| IM | anti‐cMET | Zhang et al. (2016b) | 7 | NA | IF, FISH | DAPI+/CD45−/c‐MET+, MET FISH |
0% with c‐MET CTC assay 14% (1/7) with CellSearch® |
Range 0–1 CTCs/7.5 mL (CellSearch®) |
|
IM SE |
CD45(−) | Zhang et al. (2015b) | 22a |
I (n = 2) II (n = 10) III (n = 4) IV (n = 6) |
IF, FISH | DAPI+/CD45−/CK+ and/or CEP8 signal number > 2, DAPI+/CD45−/CK− and CEP8 signal number > 2 | 68.2% (15/22) (≥ 2 CTCs) in total: 9.1% (2/22) with CK+; 59.1% (13/22) with CK−; 9.1% (2/22) (> 10 CTCs); 78.6% (11/14) (≥ 2 CTCs) in PDAC | Median 3 CTCs/3.5 mL, range 0–60 CTCs/3.5 mL, 60 CTCs/3.5 mL in a Pt with stage II, 14 CTCs/3.5 mL in a Pt with stage IV |
|
IM SE |
CD45 (−) | Wu et al. (2018) | 19 |
IIA (n = 3) IIB (n = 11) III (n = 4) IV (n = 1) |
IF, FISH | DAPI+/CD45−/CK+ and/or CEP8 signal number > 2 | 26.3% (5/19) CTMs in total: 21.1% (4/19) at baseline; 27.3% (3/11) in stage IIB; 25% (1/4) in stage III; 100% (1/1) in stage IV | Median 5 CTCs/7.5 mL (at baseline), range 1–30 CTCs/7.5 mL (at baseline) |
|
IM SE |
CD45 (−) | Gao et al. (2016) | 25 |
I (n = 5) II (n = 8) III (n = 6) IV (n = 6) |
IF, FISH | DAPI+/CD45−/CK18 + or CEP8 signal number > 2 | 88% (22/25) | Median 3 CTCs/7.5 mL, range 0–13 CTCs/7.5 mL |
|
IM MACS |
CD45 (−) | Zhang et al. (2015a) | 13 | NA | IF, Aptamer, FISH | DAPI+/CD45−/panCK+, DAPI+/CD45−/BC‐15+ | 84.6% (11/13) | Mean 34.4 CTCs/7.5 mL (panCK+), mean 24 CTCs/7.5 mL (BC‐15 + ) |
| Ren et al. (2011) | 41 | III‐IV | IF | DAPI+/CA19‐9 + /CK+ | 80.5% (33/41) (≥ 2 CTCs) | Mean 16.8 ± 16.0 CTCs/7.5 mL, range 0–59 CTCs/7.5 mL | ||
|
SLB, μF CMx chip |
EpCAM | Chang et al. (2016) | 63 |
I (n = 1) II (n = 32) III (n = 10) IV (n = 20) |
IF | DAPI+/CD45−/panCK+ |
81% (51/63) CTCs 81% (51/63) CTMs (multiple cells ≥ 2 CTCs) |
Mean 70.2 CTCs/2 mL, mean 29.5 CTMs/2 mL |
| Tien et al. (2016) | 41 | IA‐III | IF | DAPI+/CD45−/panCK+ |
39% (16/41) in PB 58.5% (24/41) in PV |
(1) In PB, mean CTCs 92.0/2 mL, median CTCs 52.0/2 mL. (2) In PV, mean CTCs 313.4/2 mL, median CTCs 116.5/2 mL | ||
| IM, μF Parallel flow micro aperture chip |
EpCAM anti‐CEA Size‐based filtration |
Chang et al. (2015) | 12a | IV | IF | DAPI+/CD45−/CK+ | 91.7% (11/12) | Mean 26 ± 11 CTCs/8 mL, range 0–42 CTCs/8 mL, mean 31 CTCs/8 mL (untreated Pts), mean 22 CTCs/8 mL (treated Pts) |
|
μF Nanostructured capture NanoVelcro chip |
EpCAM | Court et al. (2018) | 100 |
I (n = 9) II (n = 31) III (n = 31) IV (n = 29) |
IF | DAPI+/CD45−/CK+ | 78% (78/100): 44.4% (4/9) in stage I; 74.2% (23/31) in stage II; 77.4% (24/31) in stage III; 93.1% (27/29) in stage IV | Median 2 (IQR 1–6) CTCs/4 mL in total, median 7 (IQR 3–13) CTCs/4 mL in occult metastatic Pts |
|
μF Micropost GEDI |
Size‐based filtration EpCAM |
Rhim et al. (2014) | 11 |
I (n = 1) IIA (n = 1) IIB (n = 1) III (n = 1) IV (n = 7) |
IF | DAPI+/CD45−, DAPI+/CD45−/CK+ |
73% (8/11) in PDAC 40% (8/21) in Cystic lesion |
Mean 14.1 ± 18.1 CTCs/mL (PDAC), mean 4.5 ± 7.3 CTCs/mL (Cystic lesion) |
|
μF Cell surface capture GEM |
EpCAM | Sheng et al. (2014) | 18a | IV | IF | DAPI+/CD45−/CK+ | 94.4% (17/18) | Range 0–23 CTCs/7.5 mL |
|
μF Cell surface capture BioFluidica |
EpCAM | Kamande et al. (2013) | 12 |
R (n = 5) M (n = 7) |
IF | DAPI+/CD45−/EpCAM+ | 100% (7/7) in M | Mean 53CTCs/mL in M, median 51 CTCs/mL in M, range 9–95 CTCs/mL in M, mean 11 CTCs/mL in R |
| μF Cell surface capture Slit filtrationeDAR |
EpCAM Size‐based filtration |
Zhao et al. (2013) | 10a | IV | IF | Hoechst+/CD45 + /EpCAM+/CK+ | 80% (8/10) | Range 2–872 CTCs/mL |
| Size‐based filtration ISET | Pore size 8.0 μm | Poruk et al. (2016) | 50 | I (n = 8) II (n = 38)IV (n = 4) |
IF | DAPI+/CD45−/panCK+, DAPI+/CD45−/vimentin+ |
78% (39/50) with eCTCs 52% (26/50) with mCTCs |
Median 30 eCTCs/mL, range 1–251 eCTCs/mL, median 3 mCTCs/mL, range 1–16 mCTCs/mL |
| Khoja et al. (2012) | 53 |
M or Inoperable |
Light microscope, IHC | CD45−, Morphology |
88.9% (24/27) (ISET) 39.6% (21/53) (CellSearch®) |
Mean 26 CTCs/7.5 mL (ISET), median 9 CTCs/7.5 mL (ISET), range 0–240 CTCs/7.5 mL (ISET), mean 2 CTCs/7.5 mL (CellSearch®), median 0 CTCs/7.5 mL (CellSearch®) range 0–15 CTCs/7.5 mL (CellSearch®) | ||
| Size‐based filtration ScreenCell | Pore size 7.5 μm | Sefrioui et al. (2017) | 58a |
L (n = 16) LA (n = 18) M (n = 24) |
Light microscope | Morphology | 56% (33/49) in available samples: 57% (16/28) in L‐LA; 81% (17/21) in M | Median 1 CTC/mL, range 0–151 CTCs/mL |
| Kulemann et al. (2016) | 21 |
IIA (n = 2) IIB (n = 8) III (n = 4) IV (n = 7) |
IF, Light microscope, IHC, PCR | Hoechst+/CK+, Hoechst+/ZEB‐1 + , Morphology, KRAS |
86% (18/21) including KRAS
mut: 100% (2/2) in Stage IIA; 75% (6/8) in Stage IIB; 75% (3/4) in Stage III; 100% (7/7) in Stage IV 66.7% (14/21) with cytology only 23.8% (5/21) CTC clusters 57.1% (4/7) ZEB1 + in Stage IV |
Mean 0.5 CTCs/3 mL, range 0–37 CTC/3 mL | ||
| Cauley et al. (2015) | 105 | IA‐IV | Light microscope | Morphology | 49% (51/105) | NA | ||
| Kulemann et al. (2015) | 11 |
IIB (n = 4) III (n = 3) IV (n = 4) |
Light microscope, RT–PCR | Morphology, KRAS |
18% (2/11) with cytology 73% (8/11) with KRAS mut: 75% (3/4) in Stage IIB; 100% (3/3) in Stage III; 50% (2/4) in Stage IV |
NA | ||
| Iwanicki‐Caron et al. (2013) | 27 |
R (n = 9) LA (n = 9) M (n = 9) |
Light microscope | Morphology | 55.6% (15/27) in total: 44.4% (4/9) in R; 66.7% (6/9) in LA; 55.6% (5/9) in M | NA | ||
| Size‐based filtration FMSA (vs. CellSearch®) | Microfiltration | Ma et al. (2015) | 2a |
IIB (n = 1) IV (n = 1) |
Ad5GTSe infection/GFP, IF | GFP+, CK+/CD45− | 100% (2/2) (FMSA), 50% (1/2) (CellSearch®) | 13–30 CTCs/7.5 mL (FMSA), 0–1 CTCs/7.5 mL (CellSearch®) |
|
Size‐based filtration MetaCell |
Pore size 8.0 μm | Bobek et al. (2014) | 17 |
I (n = 1) IIA (n = 4) IIB (n = 4) III (n = 5) IV (n = 3) |
IF, Light microscope, IHC | DAPI+/CK18 + , Morphology, MGS, CK, CEA, Vimentin | 76.5% (13/17) in total: 78.6% (11/14) in Stage I‐III; 66.7% (2/3) in Stage IV | NA |
| Density Gradient Ficoll‐Paqueplus |
Density Gradient | Gorner et al. (2015) | 6 |
II (n = 2) III (n = 1) IV (n = 3) |
FACS RT–PCR |
Hoechst+/CD45−/EpCAM+, Integrin+, or MUC+, c‐MET, AGR2, EpCAM, Krt‐19, CD45 | 66.6% (4/6): 66.6% (2/3) in Stage II‐III; 66.6% (2/3) in Stage IV | NA |
| CAM assay | Premasekharan et al. (2016) | 2 | IV | FACS | DAPI+/CD45−/CAMhigh/CD14low | 100% (2/2) | NA | |
| oHSV1‐hTERT‐GFP |
Telomerase RT positive cancer cells GFP+ (viable cells) |
Zhang et al. (2016a) | 17 |
IIB (n = 1) III (n = 4) IV (n = 12) |
IF FACS |
CD45−/GFP+ | 88.2% (15/17) | Mean 43.1 CTCs/4 mL |
| No enrichment | Marrinucci et al. (2012) | 18a | IV | IF | DAPI+/CD45−/CK+ | 61% (11/18) (≥ 2 CTCs), 50% (9/18) (≥ 5 CTCs) | Mean 15.8 CTCs/mL |
CAM, cell adhesion matrix; CTC, circulating tumor cell; CTM, Circulating tumor microemboli; eCTC, epithelial‐like CTC; FISH, fluorescent in situ hybridization; IF, immunofluorescence; IHC, immunohistochemistry; IM, immunomagnetic; IQR, interquartile range; LA, locally advanced; M, metastatic; mCTC, mesenchymal‐like CTC; N, number of patients; NA, not available; PB, peripheral blood; PDAC, pancreatic ductal adenocarcinoma; PV, portal vein; R, resectable; RCA, rolling‐circle amplification using padlock probe; RCP, rolling‐circle product; Refs, references; SE, subtraction enrichment; SLB, supported lipid bilayer; Tx, treatment; Pt, patient; μF, microfluidic.
a
Various tumor types of pancreatic cancers are included.