Table 1.
Studies evaluating CTCs in pancreatic ductal adenocarcinoma (PDAC) including survival analysis.
| Study | Country | n | Tumor Stage | Methodology | CTC Detection Rate * | Outcome | Finding |
|---|---|---|---|---|---|---|---|
| Soeth et al., 2005 [43] | Germany | 172 | All stages, mostly IV | Density gradient separation | 34% | OS | CTC+: poor OS |
| Hoffmann et al., 2007 [41] | Germany | 37 | All stages | Density gradient separation | 40% | OS | CTC+: Trend for worse OS |
| Kurihara et al., 2008 [56] | Japan | 26 | Stage III and IV | CellSearch® | 42% | OS | CTC+: sig. worse OS |
| Sergeant et al., 2011 [42] | Belgium | 48 | All stages, 40 resectable | RT-PCR (EpCAM) | 25% preoperative 65% postoperative |
OS | No correlation between CTC and survival |
| Khoja et al., 2012 [26] | United Kingdom | 54 | 54% non-resectable | ISET®; CellSearch® | 46%/40% | OS; PFS | ISET® detects more CTCs, trend towards decreased OS |
| De Albuquerque et al., 2012 [57] | Germany | 34 | All stages (II–IV) | Immunomagnetic (EPCAM) | 47% | PFS | CTC + worse PFS |
| Bidard et al., 2013 [30] | France | 79 | Non resectable | CellSearch® | 11% | OS | CTC+ worse OS |
| Bissolati et al., 2015 [58] | Italy | 20 | Resectable Stage IIa and b | CellSearch® | 45% | OS; PFS | No correlation to OS or PFS but slightly higher liver metastasis rate in CTC+ |
| Zhang et al., 2015 [59] | China | 22 | Stage I–IV, all resectable | Immunomagnetic (CEP 8/ CD45) | 15% | OS | CTC+: worse OS |
| Earl et al., 2015 [60] | Spain | 35 | Stage II–IV | CellSearch® | 20% | OS | CTC*: worse OS, almost only metastatic disease |
| Poruk et al., 2016 [54] | USA | 60 | All stages | ISET® | 90% | OS, PFS | Epithelial CTC+: worse OS Epithelial CTC+: earlier recurrence |
| Gao et al., 2016 [53] | China | 25 | All stages | CD45 depletion and SE-FISH | I+II: 92.3% III + IV: 83.3% | OS | Patients with lower CTC count better OS than patients with high numbers of CTC |
| Kulemann et al., 2017 [31] | Germany | 58 | All stages | ScreenCell® | 68% | OS | CTC+: Trend to worse OS |
| Okubo et al., 2017 [52] | Japan | 65 | III–IV | CellSearch® | 21% | OS | CTC+ worse OS, more CTC+ in pat. Liver metastases, CTC+ after treatment neg. prong. Factor. |
| Poruk et al., 2017 [55] | USA | 60 | All stages mainly I and II |
ISET® | 78% | OS, PFS | CTC labeled with TIC (tumor initiating cell) are predictive of decreased OS and PFS |
| Gemenetzis et al., 2018 [61] | USA | 165 | All stages | ISET® | 95% of resectable patients (n = 136) | Identification of mesenchymal-mal and epithelial CTC OS; PFS |
Higher CTC counts correlate with earlier recurrence Increase of CTC numbers after neoadjuvant treatment CTC+ correlates with early recurrence and OS in the pretreated group. |
| Court et al., 2018 [27] | USA | 100 | All stages 71 localized, 29 metastatic | Nano Velcro Chip enumeration | 78% | Identification of occult metastasis; OS | CTC counts correlated with stage and worse OS |
* A cut off for CTCs in order to predict prognosis has not been established yet. In different studies, varying amounts of blood and cut offs were used. Maestro et al. detected >2 CTCs/7.5 mL as a prognostically-usable cut off, and others defined this cut off as >1/7.5 mL [26,30]. SeFish: immunostaining-fluorescence in situ hybridization.