Table 1.
Summary of head and neck CTC studies.
Study | N | Study design | Treatment population (stage) | Method of detection | When CTCs measured | Range CTCs | Marker | % With CTCs | Mean Follow-up, months | Outcome (+)CTC: (−) CTC | Other outcomes |
---|---|---|---|---|---|---|---|---|---|---|---|
Wirtshafter et al (2002)14 | 18 | Prospective | Ⅰ–Ⅳ | Positive Selection ICC | Before treatment | 0–3 | EpCAM | 44% | N/A | Outcomes not examined | |
Partridge et al (2003)34 | 36 | Prospective | Ⅰ–Ⅳ | Negative Depletion ICC and RT-PCR | Before, after surgery | 0–5 | Pan-CK, E48 | 50% | 36 | Reduced DFS | Poor agreement between RT-PCR and ICC |
Winter et al (2009)35 | 16 | Prospective | Ⅰ–Ⅳ | RT-PCR | Before, after surgery | N/A | EGFR, CK, ELF3, Eph84 | 63% | N/A | No difference | |
Jatana et al (2010)26 | 48 | Prospective | Ⅰ–Ⅳ | Negative Depletion ICC | Before treatment | 0–3300 | CK | 71% | 19 | Reduced DFS | |
Hristozova et al (2011)29 | 42 | Prospective | LR advanced | Flow cytometry and RT-PCR | Before treatment | 0–4 | EpCAM, CK | 43% | N/A | Assoc with ≥N2b disease | Decrease in CTC with chemoradiation |
Nichols et al (2011)24 | 15 | Prospective | Ⅲ–Ⅳ | CellSearch (Positive Selection ICC) | Before treatment | 0–2 | EpCAM | 40% | N/A | CTC presence assoc. with lung nodules >1 cm; reduced survival | |
Buglione et al (2012)23 | 73 | Prospective | HNSCC and SNUC (Ⅰ–Ⅳ) | CellSearch (Positive Selection ICC) | Before, during, after treatment | 0–43 | EpCAM | 15% | 14 | No difference | Decrease in CTC over treatment correlated with response; CTCs presence trended positively with increasing stage (NS) |
Bozec et al (2013)22 | 49 | Prospective | Ⅲ–Ⅳ | CellSearch (Positive Selection ICC) | N/A | 0–5 | EpCAM | 16% | 6 | No difference | |
Hseih et al (2014)33 | 53 | Prospective | LR advanced, recurrent, metastatic | Negative Depletion ICC | Before treatment | N/A | EpCAM | 19% | 10.5 | PDPN+/EpCAM + ratio >20% prognostic factor for DSM | |
Grisanti et al (2014)32 | 53 | Prospective | Recurrent/Metastatic | CellSearch (Positive Selection ICC) | Before, during, after treatment | 0–43 | EpCAM | 26% baseline; 41% at any point | 25 | Reduced PFS and OS | |
Tinhofer et al (2014)36 | 144 | Prospective | Ⅲ–Ⅳ | RT-PCR | After surgery, before adjuvant | N/A | EpCAM, CK | 29% | 34 | Reduced DFS and OS in Non-OPSCCa; opposite effect in OPSCC | No assoc. between CTC presence and HPV in OPSCCa |
Inhestern et al (2015)25 | 40 | Prospective | Ⅱ–Ⅳ | Flow cytometry | Before, during, after treatment | 0–11298 | EpCAM | 80% baseline; 97% at any point | 23 | Baseline CTCs > median = reduced RFS and Maximal CTCs at any point > median = reduced OS | Overall CTCs decreased during IC; increased after surgery; decreased after radiotherapy |
ICC: immunocytochemistry; EpCAM: epithelial cell adhesion molecule; RT-PCR: reverse transcriptase – polymerase chain reaction; CK: cytokeratin; DFS: disease free survival; EGFR: epidermal growth factor receptor; LR: locoregional; CTC: circulating tumor cell; HNSCC: head and neck squamous cell carcinoma; SNUC: sinonasal undifferentiated carcinoma; NS: not significant; PDPN: podoplanin; OS: overall survival; OPSCC: oropharyngeal squamous cell carcinoma.