Background
Methods
Search strategy
Study eligibility criteria
Data extraction and quality assessment
Statistical analysis
Ethics statement
Results
Baseline characteristics of the included studies
Reference | Number (M/F) | C/R/RS | ST | CRT before and after ST | Age mean ± SD/ median (range) | Methods | Rate(+) | Follow up mean ± SD/median (range) | Tumor stage | HR (method no.) | OM | Surgery |
---|---|---|---|---|---|---|---|---|---|---|---|---|
Barbazan 2014 [30] | 50(37/13) | 34/14 | baseline | NO/YES | 64.5 ± 10.3; 31-84 | RT-PCR | 13/50 | 0-40 | mCRC | PFS,OS(3) | PFS,OS, | NR |
4 W; 16 W | YES/YES | 64.5 ± 10.3; 31-84 | RT-PCR | 12/50; 15/50 | 0-40 | mCRC | PFS,OS(3); PFS,OS(11) | PFS,OS, RECIST | NR | |||
Kuboki 2013 [34] | 63(34/29) | 41/22/0 | baseline | NO/YES | 61(33–81) | Cellsearch | 19/63 | median:8.7 | mCRC | PFS,OS(3) | PFS,OS, RECIST | NR |
Lu 2013 [36] | 90(51/39) | 90/0/0 | 1,4 W | YES/YES | 63.1 ± 12.9 | membrane-array | 21/90 | 36(18–61) | III stage | PFS,OS(3) | PFS,OS | YES |
Iinuma(1) 2013 [35] | Training: 420(224/196) | NR | baseline | NO/YES | 66.0 ± 12.4 | RT-PCR | 57/150 | 36.9 ± 19.5 | Dukes’ C | PFS,OS(3) | PFS,OS | YES |
Iinuma(2) 2013 [35] | Validation: 315(175/140) | NR | baseline | NO/YES | 67.5 ± 11.8 | RT-PCR | 35/97 | 37.1 ± 18.1 | Dukes’ C | PFS,OS(3) | PFS,OS | YES |
Sastre 2012 [26] | 180(118/62) | 121/40/19 | baseline | NO/YES | 65(40–82) | Cellsearch | 85/180 | 29(0–53.2) | mCRC | PFS,OS(3) | PFS,OS, RECIST | 123YES |
147 | NR | cycle3 | YES/YES | NR | Cellsearch | 23/147 | NR | mCRC | PFS,OS(3) | PFS,OS, RECIST | 123YES | |
de Albuquerque 2012 [27] | 60(43/17) | NR | baseline | NO/YES | 65.2(40–80) | RT-PCR | 23/33 | 8.1(6.4-9.7) | II-IV stage | PFS(10) | PFS, RECIST | NR |
33 | NR | 1-4 W; 5-8 W; 9-12 W | YES/YES | NR | RT-PCR | 18/33; 19/33; 17/33 | NR | NR | NR | RECIST | NR | |
Matsusaka 2011 [28] | 64(31/33) | 36/28 | baseline | NO/YES | 59(18–72) | Cellsearch | 12/64 | 0-36 | mCRC | PFS(3);OS(10) | PFS,OS, RECIST | NR |
/ | NR | 2 W; 8-12 W | YES/YES | NR | Cellsearch | 7/63; 4/60 | NR | mCRC | PFS(3);OS(10) | PFS,OS, RECIST | NR | |
Konigsberg 2010 [33] | 38(23/15) | NR | mixed | NO/YES | 65(44–82) | ICC | 23/38 | 11.7(8.4-14.9) | mCRC | PFS,OS(3) | PFS,OS, RECIST | NR |
Yalcin 2010 [32] | 93(50/43) | NR | mixed | part NO/YES | 56(24–78) | Cellsearch | 30/93 | 6 | II-IV stage | NR | RECIST | PART YES |
Tol 2010 [29] | 467(284/183) | 225/122/120 | baseline | NO/YES | 63(27–83) | Cellsearch | 129/451 | 16.8 | mCRC | PFS,OS(3) | PFS,OS, RECIST | NO |
/ | NR | 1-2 W | YES/YES | NR | Cellsearch | 21/368 | NR | mCRC | PFS,OS(3) | PFS,OS, RECIST | NR | |
/ | NR | 3-5 W; 6-12 W; 13-20 W | YES/YES | NR | Cellsearch | 17/320; 18/336; 16/254 | NR | mCRC | PFS,OS(3) | PFS,OS, RECIST | NR | |
Yen 2009 [37] | 76(44/32) | 55/21 | NR | NR | 64(39–83) | membrane-array | 30/76 | 20(4–34) | mCRC | PFS,OS(3) | PFS,OS, RECIST | YES |
Cohen 2008 [11] | 430(238/192) | 292/71/66 | baseline | NO/YES | 64(22–92) | Cellsearch | 107/413 | 12.6 ± 6.5/11.0(0.8-30.0) | mCRC | PFS,OS(11) | PFS,OS, RECIST | NR |
/ | NR | 3-5 W | YES/YES | NR | Cellsearch | 38/320 | NR | mCRC | PFS,OS(11) | PFS,OS, RECIST | NR | |
/ | NR | 1-2 W; 6-12 W; 13-20 W | YES/YES | NR | Cellsearch | 41/357; 25/310; 21/193 | NR | mCRC | PFS,OS(11) | PFS,OS, RECIST | NR | |
Staritz 2004 [31] | 42 | NR | baseline | NO/YES | NR | RT-PCR | 19/41 | 13.7(1.9-25.4) | mCRC | OS(10) | OS | NR |
1 day | YES/YES | NR | RT-PCR | 23/40 | 13.7(1.9-25.4) | mCRC | OS(10) | OS | NR |
Study | Selection (0–4) | Comparability (0–2) | Outcome (0–3) | Total | ||||||
---|---|---|---|---|---|---|---|---|---|---|
REC | SNEC | AE | DO | SC | AF | AO | FU | AFU | ||
Barbazan 2014 [30] | 0 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 5 |
Kuboki 2013 [34] | 0 | 1 | 1 | 1 | 0 | 0 | 1 | 0 | 0 | 4 |
Lu 2013 [36] | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 1 | 7 |
Iinuma 2013 [35] | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 6 |
Sastre 2012 [26] | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 6 |
de Albuquerque 2012 [27] | 0 | 1 | 1 | 1 | 0 | 0 | 1 | 0 | 1 | 5 |
Matsusaka 2011 [28] | 0 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 0 | 6 |
Konigsberg 2010 [33] | 0 | 1 | 1 | 1 | 0 | 0 | 1 | 0 | 0 | 4 |
Yalcin 2010 [32] | 0 | 1 | 1 | 1 | 0 | 0 | 1 | 0 | 0 | 4 |
Tol 2010 [29] | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 6 |
Yen 2009 [37] | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 6 |
Cohen2008 [11] | 0 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 5 |
Staritz 2004 [31] | 0 | 1 | 1 | 1 | 0 | 0 | 1 | 0 | 1 | 5 |
Correlation of CTCs with the objective response to chemotherapy
Sample time | Method | CellSearch | |||||
---|---|---|---|---|---|---|---|
Any | Baseline | During-chemotherapy | CellSearch | No-Cellsearch | Baseline | During- chemotherapy | |
Response rate(RRi) ¶ii
| 1.740[0.878-3.447], I
2
= 75.4% | 1.258[0.990-1.598], I
2
= 6.9%;Fixed:1.263 [1.008-1.584],I
2
= 6.9% | 2.315[1.242-4.316], I
2
= 0% | 1.326[0.904-1.946],I
2
= 22.5% | 5.2174 [2.3258-11.7041], N = 1iii
| 1.258[0.990-1.598], I
2
= 6.9%;Fixed:1.263 [1.008-1.584],I
2
= 6.9% | 2.315[1.242-4.316],I
2
= 0% |
Disease control rate(RR) Ψiv
| 1.354[1.002-1.830], I
2
= 80.8% | 1.375[0.961-1.967], I
2
= 77.4% | 1.535[1.170-2.016],I
2
= 69.8% | 1.110[0.784-1.571],I
2
= 74.6% | 2.005[1.052-3.821], I
2
= 87.7% | 0.974[0.933-1.016], I
2
= 0.0% | 1.451[1.116-1.887],I
2
= 36.3% |
Disease control rate(RR) ¶ | 1.354[1.065-1.721], I2 = 59.5% | 1.248[0.874-1.783], I
2
= 74.7% | 1.331[1.099-1.612], I
2
= 35.9% | 1.292[1.005-1.660], I
2
= 42.4% | 1.933[0.633-5.902],I
2
= 86.0% | 0.974[0.933-1.016], I
2
= 0.0% | 1.451[1.116-1.887],I
2
= 36.3% |
CTCs change
| |||||||
Disease control rate (ORv: increase VS decrease) Ψ | 27.088[4.960- 147.919], I
2
= 0.0% | / | / | 39.000[2.932- 518.841], N = 1 | 20.570[2.170-194.950], N = 1 | / | / |
HRvi for PFSvii(L/H to H VS H to Lviii) ¶ | 2.095[1.105-3.969], I
2
= 74% | / | / | 2.095[1.105-3.969], I
2
= 74% | / | / | / |
HR for OS(L/H to H VS H to L) ¶ | 3.604[2.096-6.197], I
2
= 52.9% | / | / | 3.604[2.096-6.197], I
2
= 52.9% | / | / | / |
Prognosis
| |||||||
HR for PFS Ψ | 2.500[1.746-3.580], I
2
= 90.0%; Without Matsusaka 2.654[2.069-3.405], I
2
= 58.1% | 1.853[1.405-2.445], I
2
= 83.6%; Without Matsusaka 1.942[1.549-2.435], I
2
= 47.6% | 2.386[1.454-3.917],I
2
= 93.3%; Without Matsusaka 2.694[2.085-3.481], I
2
= 35.1% | 1.769[1.180-2.651],I
2
= 90.2%; Without Matsusaka 2.059[1.563-2.712], I
2
= 50.4% | 3.387[2.479-4.628],I
2
= 32.7% | 1.422[1.102-1.835], I
2
= 82.5%; Without Matsusaka 1.578[1.355-1.837], I
2
= 0% | 2.127[1.190-3.802], I
2
= 95%; Without Matsusaka 2.697[2.208-3.294], I
2
= 0% |
HR for PFS | 2.237[1.485-3.370], I
2
= 91.8%; Without Matsusaka 2.476[1.830-3.350], I
2
= 68.0% | 1.621[1.224-2.146], I
2
= 83.6% Without Matsusaka 1.736[1.383-2.180], I
2
= 44.5% | 2.100[1.273-3.465],I
2
= 93.7%; Without Matsusaka 2.593[2.152-3.124], I
2
= 0.0% | 1.769[1.180-2.651],I
2
= 90.2%; Without Matsusaka 2.059[1.563-2.712], I
2
= 50.4% | 3.618[1.976-6.624],I
2
= 65.8% | 1.422[1.102-1.835], I
2
= 82.5%; Without Matsusaka 1.578[1.355-1.837], I
2
= 0% | 2.127[1.190-3.802], I
2
= 95%; Without Matsusaka 2.697[2.208-3.294], I
2
= 0% |
Operation: HR for PFS¶ | 3.433[2.111-5.583],I
2
= 72.8% | 2.377[1.692-3.339], I
2
= 18.8% | 3.344[1.135-9.852], I
2
= 75.6% | 1.981[1.478-2.654], N = 1 | 4.265[3.079-5.907],I
2
= 0.0% | 1.943[1.362-2.770], N = 1 | 2.063[1.231-3.458], N = 1 |
HR for OSix¶ | 2.856[1.959-4.164],I
2
= 83.4%; Without Matsusaka 3.139[2.167-4.545],I
2
= 76.1% | 2.356[1.957-2.836], I
2
= 14.0%; Without Matsusaka 2.288[1.941-2.697], I
2
= 1.7% | 3.292[1.611-6.726],I
2
= 96.2%; Without Matsusaka 3.998[2.478-6.449], I
2
= 79.5% | 2.452[1.484-4.050],I
2
= 89.9%; Without Matsusaka 2.895[1.697-4.940], I
2
= 85.9% | 3.367[1.882-6.023],I
2
= 68.6% | 2.310[1.759-3.035], I
2
= 49.9%; Without Matsusaka 2.210[1.716-2.846], I
2
= 46.8% | 2.802[1.175-6.684],I
2
= 97.4%; Without Matsusaka 3.792[2.052-7.009],I
2
= 86.5% |
HR for OS¶ | 2.642[1.716-4.067],I
2
= 86.2%; Without Matsusaka 2.968[1.913-4.606],I
2
= 80.4% | 2.373[1.873-3.006], I
2
= 34.3%; Without Matsusaka 2.284[1.836-2.842], I
2
= 27.6% | 2.787[1.321-5.882],I
2
= 96.6%; Without Matsusaka 3.536[2.149-5.818],I
2
= 81.8% | 2.452[1.484-4.050], I
2
= 89.9%; Without Matsusaka 2.895[1.697-4.940],I
2
= 85.9% | 2.969[1.053-8.375],I
2
= 78.2% | 2.310[1.759-3.035], I
2
= 49.9%; Without Matsusaka 2.210[1.716-2.846], I
2
= 46.8% | 2.802[1.175-6.684],I
2
= 97.4%; Without Matsusaka 3.792[2.052-7.009],I
2
= 86.5% |
Operation: HR for OS¶ | 3.681[1.833-7.394],I
2
= 81.8% | 1.890[1.407-2.539], I
2
= 0.0% | 4.069[0.872-18.980],I
2
= 87.0% | 1.738[1.296-2.332], N = 1 | 4.678[2.267-9.654],I
2
= 67.5% | 1.642[1.149-2.345], N = 1 | 1.961[1.168-3.295], N = 1 |