Background
Methods
Search strategy
Inclusion and exclusion criteria
Data extraction and quality assessment
Statistical analysis
Results
Baseline characteristics of the eligible studies
Article | Country | Number (M/F)a
| Age Mean ± SDb/Median (range) (yc) | TSd
| Markers | Adjuvant therapy | STe
| Rate (+)f
| OMg
| HRh estimate | CSi
| MAj
|
---|---|---|---|---|---|---|---|---|---|---|---|---|
Kust 2016 [33] | Croatia | 82(49/33) | Mean:66 ± 9.6 | I-III | CK20 | Post-OPk CTl for III and part of II | Pre-OP | 22 (26.83%) | OSm
DFSn
| Data extrapolated | Yes | No |
Liu 2013 [28] | China | 92(60/32) | Mean:66 ± 9.6 | I-III | CK20 | _ | Pre-OP | 31 (25%) | OS DFS | Reported in text | Yes | Yes |
Liu 2013 (1) [28] | China | 41(NR) | NRo
| II | CK20 | Without | _ | NR | OS DFS | Reported in text | Yes | Yes |
Liu 2013 (2) [28] | China | 51(NR) | NR | III | CK20 | Post-OP CT | _ | NR | OS DFS | Reported in text | Yes | Yes |
Yokobori (1) 2013 [29] | Japan | Training: 151(86/65) | Mean:66.76 ± 11.02 | II | PLS3 | Without | Pre-OP | 33 (21.85%) | OS DFS | Reported in text | Yes | Yes |
Yokobori (2) 2013 [29] | Japan | Training: 131(75/56) | Mean:66.76 ± 11.02 | III | PLS3 | Post-OP CT | Pre-OP | 38 (29%) | OS DFS | Reported in text | Yes | Yes |
Yokobori (3) 2013 [29] | Japan | Validation: 158(96/62) | Mean:67.51 ± 11.08 | II | PLS3 | Without | Pre-OP | 35 (22.15%) | OS DFS | Reported in text | Yes | Yes |
Yokobori (4) 2013 [29] | Japan | Validation: 103(63/40) | Mean:67.51 ± 11.08 | III | PLS3 | Post-OP CT | Pre-OP | 30 (29.12%) | OS DFS | Reported in text | Yes | Yes |
Shimada (1) 2012 [19] | Japan | 111(60/51) | Median:68(27–82) | II | CEA, CK19, CK20, CD133 | Without | Post-OP | 63 (56.76%) | OS DFS | Reported in text | Yes | Yes |
Shimada (2) 2012 [19] | Japan | 86(47/39) | Median:68(27–82) | III | CEA, CK19, CK20, CD133 | Post-OP CT | Post-OP | 61 (70.93%) | OS DFS | Reported in text | Yes | Yes |
Iinuma (1) 2011 [30] | Japan | Training: 420(224/196) | Mean:66.0 ± 12.4 | I-III | CEA, CK19, CK20, CD133 | _ | Post-OP | 106(25.24%) | OS DFS | Reported in text | Yes | Yes |
Iinuma (1–1) 2011 [30] | Japan | Training: 176(NR) | NR | II | CEA, CK19, CK20, CD133 | Without | _ | NR | OS DFS | Reported in text | Yes | Yes |
Iinuma (1–2) 2011 [30] | Japan | Training:150(NR) | NR | III | CEA, CK19, CK20, CD133 | Post-OP CT | _ | NR | OS DFS | Reported in text | Yes | Yes |
Iinuma (2) 2011 [30] | Japan | Validation: 315(175/140) | Mean:66.0 ± 12.4 | I-III | CEA, CK19, CK20, CD133 | _ | Post-OP | 75(23.81%) | OS DFS | Reported in text | Yes | Yes |
Iinuma (2–1) 2011 [30] | Japan | Validation: 143(NR) | NR | II | CEA, CK19, CK20, CD133 | Without | _ | NR | OS DFS | Reported in text | Yes | Yes |
Iinuma (2–2) 2011 [30] | Japan | Validation: 97(NR) | NR | III | CEA, CK19, CK20, CD133 | Post-OP CT | _ | NR | OS DFS | Reported in text | Yes | Yes |
Uen 2008 [31] | China | 438(234/204) | NR | I-III | CK19, CK20, CEA, hTERT | Post-OP CT for III and part of II | Post-OP (1 Wp) | 137 (31.27%) | DFS | Reported in text | Yes | Yes |
Barreto 2007 [32] | UK | 113(NR) | Mean:67 | I-III | CEA, CK20 | Post-OP CT for III and part of II | Post-OP (24 hq) | 34 (30.09%) | DFS | Reported in text | Yes | Yes |
Koch 2006 [33] | Germany | 90(59/31) | Mean:66.1 | II | CK20 | Post-OP CT for rectal cancer | Post-OP | 28 (31.1%) | OS DFS | Reported in text | Yes | No |
Lloyd 2006 [34] | Australia | 125 (74/51) | Median:74 (43–95) | I-II | CK20, CEA, EphB4, LAMγ2, MAT | Without | Pre-OP | 5 (4%) | DFS | Data extrapolated | Yes | No |
Sadahrio 2005 [35] | Japan | 100(NR) | NR | I-III | CEA | NR | Intra-OP | 39 (39%) | OS DFS | Data extrapolated | Yes | Yes |
Bessa 2003 [36] | Spain | 66 (23/43) | Median:73 | I-III | CEA | Post-OP CT for III and part of II | Post-OP | 36 (54.55%) | OS DFS | Reported in text | Yes | Yes |
Ito 2002 [37] | Japan | 99(62/37) | NR | I-III | CEA | NR | Post-OP | 26 (26.26%) | DFS | Data extrapolated | Yes | No |
Study | Selection (0–4) | Comparability (0–2) | Outcome (0–3) | Total | ||||||
---|---|---|---|---|---|---|---|---|---|---|
REC | SNEC | AE | DO | SC | AF | AO | FU | AFU | ||
Kust 2016 [20] | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 0 | 4 |
Liu 2013 [28] | 0 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 5 |
Yokobori 2013 [29] | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 6 |
Shimada 2012 [19] | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 1 | 7 |
Iimuna 2011 [30] | 0 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 5 |
Uen 2008 [31] | 0 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 5 |
Barreto 2007 [32] | 0 | 0 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 4 |
Koch 2006 [33] | 0 | 1 | 1 | 1 | 0 | 0 | 1 | 0 | 0 | 4 |
Lloyd 2006 [34] | 0 | 0 | 1 | 1 | 0 | 0 | 1 | 0 | 0 | 3 |
Sadahrio 2005 [35] | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 1 | 7 |
Bessa 2003 [36] | 0 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 5 |
Ito 2002 [37] | 0 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 5 |
Effects of CTCs on OS and DFS for non-mCRC patients
Association between CTCs and clinicopathological parameters
Exploring the sources of heterogeneity
Variables | HR[95%CI] | Number | I2
| Pd
|
---|---|---|---|---|
Year > mediana
| ||||
Yes | 3.65[2.49–5.36] | 6 | 0.00% | 0.578 |
No | 2.44[1.19–4.99] | 7 | 72.90% | 0.001 |
Country | ||||
East Asia | 3.39[2.27–5.05] | 10 | 46.50% | 0.051 |
Non-East Asia | 2.10[0.52–8.54] | 3 | 74.50% | 0.02 |
Marker | ||||
Single | 2.72[1.48–5.00] | 9 | 66.80% | 0.002 |
Multiple | 3.77[2.62–5.43] | 4 | 0.00% | 0.799 |
Sampling time point | ||||
Pre-op | 3.65[2.49–5.36] | 6 | 0.00% | 0.578 |
Intra/post-op | 2.44[1.19–4.99] | 7 | 72.90% | 0.001 |
Patient no. > medianb
| ||||
Yes | 3.45[2.57–4.65] | 6 | 0.00% | 0.801 |
No | 2.59[1.08–6.22] | 7 | 74.20% | 0.001 |
Detection rate > meanc
| ||||
Yes | 1.57[0.42–5.79] | 4 | 74.10% | 0.009 |
No | 3.71[2.84–4.85] | 9 | 0.00% | 0.796 |
Quality of study | ||||
Low | 4.06[1.64–10.05] | 2 | 0.00% | 0.384 |
High | 2.95[1.87–4.65] | 11 | 61.50% | 0.004 |
Overall | 3.07[2.05–4.62] | 13 | 55.70% | 0.008 |
Variables | Coef.a
| Std. Err.b
|
P value | Adj R-squaredc
|
---|---|---|---|---|
Year | 0.5072 | 0.4559 | 0.2900 | 0.67% |
Country | 0.5352 | 0.5770 | 0.3740 | 1.08% |
Marker | 0.4133 | 0.5021 | 0.4280 | −11.42% |
Time point | −0.5072 | 0.4559 | 0.2900 | 0.67% |
Patient no. | 0.3751 | 0.4688 | 0.4410 | −10.13% |
Detection rate(mean) | −1.1526 | 0.4288 | 0.0210 | 93.80% |
Quality of study | −0.3412 | 0.7123 | 0.6410 | −12.93% |