Introduction
Materials and methods
Literature search strategy
Inclusion and exclusion criteria
Data extraction
Quality assessment
Statistical analysis
Results
Literature search results and characteristics of included studies
Trial | Time Range | Region | Treatment | Sample size | Median follow-up | Median Age | pStage | Histology | CT | RT | RT |
---|---|---|---|---|---|---|---|---|---|---|---|
regimen | dose (Gy) | technique | |||||||||
NEOCRTEC5010/2018 [5] | 2007–2014 | China | nCRTS-IFI | 224 | 41 m | 56 | I-IV | SCC | NP | 40 | 3D |
S alone | 227 | 58 | |||||||||
2004–2008 | Netherlands | nCRTS-IFI | 178 | 84 m | 60 | I-III | SCC/AC | PC | 41.4 | 3D | |
S alone | 188 | 60 | |||||||||
Lv/2010 [8] | 1997–2004 | China | nCRTS-IFI | 80 | 45 m | NR | I-III | SCC | PC | 40 | 2D |
S alone | 80 | ||||||||||
FFCD9901/2014 [9] | 2000–2009 | France | nCRTS-IFI | 98 | 94 m | 58.1 | I-III | SCC/AC | FP | 45 | 3D |
S alone | 97 | 57.6 | |||||||||
IG9401/2005 [10] | 1994–2000 | Australia | nCRTS-IFI | 128 | 65 m | 61 | NR | SCC/AC | FP | 35 | 2D |
S alone | 128 | 62 | |||||||||
Urba/2001 [11] | 1985–1987 | America | nCRTS-IFI | 50 | 98 m | 62 | NR | SCC/AC | FP + Vin | 45 | 3D |
S alone | 50 | 64 | |||||||||
Bosset/1997 [12] | 1989–1995 | France | nCRTS-IFI | 143 | 55 m | 56.6 | I-III | SCC | Cis | 37 | 3D |
S alone | 139 | 56.7 | |||||||||
1990–1995 | Ireland | nCRTS-IFI | 58 | 10 m | 65 | I-IV | AC | FP | 40 | 2D | |
S alone | 55 | 65 | |||||||||
Apinop/1994 [15] | 1986–1992 | Thailand | nCRTS-IFI | 35 | NR | 59.6 | NR | SCC | FP | 40 | 2D |
S alone | 34 | 59.8 | |||||||||
Cao/2009 [16] | 1991–2000 | China | nCRTS-IFI | 118 | NR | NR | II-IV | SCC | FP | 40 | 2D |
nCTS | 119 | ||||||||||
S alone | 118 | ||||||||||
Yanagi/2018 [17] | 1997–2001 | Japan | nCRTS-ENI | 20 | 90 m | 61.5 | I-IV | SCC | FP | 40 | NR |
S alone | 21 | 60 | |||||||||
CALGB9781/2008 [18] | 1997–2000 | America | nCRTS-ENI | 30 | 72 m | 59.9 | NR | SCC/AC | FP | 50.4 | 3D |
S alone | 26 | 62.2 | |||||||||
Natsugoe/2006 [19] | 1997–2001 | Japan | nCRTS-ENI | 22 | 24 m | NR | II-IV | SCC | FP | 40 | NR |
S alone | 23 | ||||||||||
Lee/2004 [20] | 1999–2002 | Korea | nCRTS-ENI | 51 | 25 m | 63 | I-IV | SCC | FP | 45.6 | 2D |
S alone | 50 | 63 | |||||||||
Le Prise/1994 [21] | 1988–1991 | France | nCRTS-ENI | 41 | 16 m | 56 | NR | SCC | FP | 20 | 2D |
S alone | 45 | 59 | |||||||||
Nygaard/1992 [22] | 1983–1988 | Norway | nCRTS-ENI | 53 | NR | 60.1 | NR | SCC | Cis + Ble | 35 | 2D |
nCTS | 56 | 62.9 | |||||||||
S alone | 50 | 61.4 | |||||||||
2000–2005 | Germany | nCRTS-ENI | 60 | 126 m | 60.6 | I-IV | AC | PLF | 30 | 3D | |
nCTS | 59 | 56 | |||||||||
Burmeister/2011 [37] | 2000–2006 | Australia | nCRTS-IFI | 39 | 94 m | 60 | I-III | AC | FP | 35 | 3D |
nCTS | 36 | 63 | |||||||||
Boonstra/2011 [38] | 1989–1996 | Netherlands | nCTS | 85 | 15 m | 60 | I-IV | SCC | EP | ||
S alone | 84 | 14 m | 60 | ||||||||
Ychou/2011 [39] | 1995–2003 | Multicenter | nCTS | 84 | NR | NR | NR | AC | FP | ||
S alone | 85 | ||||||||||
1992–1998 | UK | nCTS | 400 | 73 m | 63 | NR | SCC/AC | FP | |||
S alone | 402 | 63 | |||||||||
MAGIC/2006 [42] | 1994–2002 | Multicenter | nCTS | 65 | NR | NR | NR | AC | ECF | ||
S alone | 66 | ||||||||||
1990–1995 | Multicenter | nCTS | 233 | NR | 61 | NR | SCC/AC | FP | |||
S alone | 234 | 62 | |||||||||
Ancona/2001 [45] | 1992–1997 | Italy | nCTS | 47 | NR | 58 | NR | NR | FP | ||
S alone | 47 | 58 | |||||||||
Baba/2000 [46] | 1993–1995 | Japan | nCTS | 21 | NR | 63.6 | I-IV | SCC | PLF | ||
S alone | 21 | 60.1 | |||||||||
Law/1997 [47] | 1989–1995 | China | nCTS | 74 | 17 m | 64 | I-III | SCC | FP | ||
S alone | 73 | 63 | |||||||||
Schlag/1992 [48] | NR | Germany | nCTS | 35 | 8 m | NR | NR | SCC | FP | ||
S alone | 42 | ||||||||||
Maipang/1994 [49] | 1988–1990 | Thailand | nCTS | 24 | NR | 64.2 | NR | SCC | Cis + Ble | ||
S alone | 22 | 64.8 | |||||||||
Roth/1988 [50] | 1982–1986 | America | nCTS | 19 | 30 m | NR | NR | NR | NP + Ble | ||
S alone | 20 |
Assessment of included trial
Conventional pairwise meta-analysis
Outcome | Treatment | No. of studies | No. of patients | HR/OR(95%CI) | Heterogeneity | |
---|---|---|---|---|---|---|
I2(%) |
P
| |||||
OS | nCRTS-ENI vs S alone | 6 | 432 |
HR 0.70(0.54–0.92)
| 8 | 0.37 |
nCRTS-IFI vs S alone | 10 | 2228 |
HR 0.74(0.66–0.83)
| 10 | 0.35 | |
nCTS vs S alone | 13 | 2526 |
HR 0.86(0.76–0.98)
| 40 | 0.06 | |
LR | nCRTS-ENI vs S alone | 4 | 288 | OR 0.69(0.35–1.35) | 46 | 0.13 |
nCRTS-IFI vs S alone | 6 | 1221 |
OR 0.43(0.33–0.57)
| 0 | 0.50 | |
nCTS vs S alone | 7 | 2176 |
OR 0.79(0.62–0.99)
| 26 | 0.23 | |
DM | nCRTS-ENI vs S alone | 4 | 288 | OR 0.87(0.35–2.21) | 57 | 0.07 |
nCRTS-IFI vs S alone | 6 | 1221 |
OR 0.79(0.62–1.00)
| 0 | 0.43 | |
nCTS vs S alone | 7 | 2176 |
OR 0.83(0.68–1.01)
| 37 | 0.15 | |
R0 resection | nCRTS-ENI vs S alone | 2 | 155 |
OR 5.75(2.19–15.13)
| 0 | 0.61 |
nCRTS-IFI vs S alone | 4 | 1119 |
OR 5.17(1.95–13.67)
| 68 | 0.02 | |
nCTS vs S alone | 7 | 1705 |
OR 1.71(1.39–2.10)
| 0 | 0.75 | |
nCRTS-ENI vs nCT | 2 | 166 |
OR 4.71(1.98–11.24)
| 0 | 0.85 | |
POM | nCRTS-ENI vs S alone | 5 | 324 | OR 1.52(0.66–3.52) | 0 | 0.85 |
nCRTS-IFI vs S alone | 8 | 1704 |
OR 1.79(1.14–2.82)
| 27 | 0.21 | |
nCTS vs S alone | 11 | 2453 | OR 1.02(0.75–1.38) | 0 | 0.87 |
Network meta-analysis
a. Network meta-analysis results for five outcomes | |||||
OS | |||||
nCRTS-ENI | |||||
0.84(0.62–1.1) | nCRTS-IFI | ||||
0.73(0.55–0.97)
| 0.87(0.73–1.0) | nCTS | |||
0.63(0.48–0.83)
|
0.75(0.66–0.86)
|
0.87(0.77–0.97)
| S-alone | ||
LR | |||||
nCRTS-IFI | |||||
0.74(0.37–1.5) | nCRTS-ENI | ||||
0.59(0.37–0.94)
| 0.61(0.30–1.3) | nCTS | |||
0.43(0.30–0.60)
| 0.58(0.31–1.1) | 0.79(0.59–1.1) | S-alone | ||
DM | |||||
nCRTS-IFI | |||||
1.0(0.54–1.9) | nCRTS-ENI | ||||
0.92(0.60–1.4) | 0.90(0.50–1.6) | nCTS | |||
0.79(0.57–1.1) | 0.76(0.44–1.3) | 0.85(0.64–1.2) | S-alone | ||
POM | |||||
S-alone | |||||
0.99(0.68–1.4) | nCTS | ||||
0.56(0.33–0.92)
| 0.56(0.30–1.0) | nCRTS-IFI | |||
0.56(0.27–1.1) | 0.56(0.27–1.2) | 1.0(0.41–2.4) | nCRTS-ENI | ||
R0 resection | |||||
S-alone | |||||
0.57(0.40–0.80)
| nCTS | ||||
0.16(0.09–0.28)
|
0.28(0.14–0.53)
| nCRTS-IFI | |||
0.16(0.07–0.34)
|
0.29(0.13–0.59)
| 1.0(0.39–2.6) | nCRTS-ENI | ||
b. Network meta-analysis results of OS for four subgroups | |||||
ESCC | |||||
nCRTS-IFI | |||||
0.83(0.47–1.5) | nCRTS-ENI | ||||
0.78(0.63–0.96)
| 0.80(0.43–1.5) | nCTS | |||
0.50(0.38–0.68)
| 0.61(0.35–1.0) | 0.76(0.57–1.0) | S-alone | ||
EAC | |||||
nCRTS-ENI | |||||
0.70(0.37–1.3) | nCRTS-IFI | ||||
0.65(0.38–1.1) | 0.93(0.71–1.3) | nCTS | |||
0.50(0.28–0.87)
|
0.72(0.58–0.91)
|
0.78(0.62–0.93)
| S-alone | ||
RT with dose of ≥40Gy/<40Gy | |||||
nCRTS-ENI ≥ 40Gy | |||||
0.90(0.59–1.4) | nCRTS-IFI ≥ 40Gy | ||||
0.89(0.54–1.5) | 0.99(0.70–1.4) | nCRTS-ENI < 40Gy | |||
0.71(0.48–1.1) | 0.79(0.65–0.96) | 0.80(0.58–1.1) | nCTS | ||
0.68(0.43–1.1) | 0.76(0.56–1.0) | 0.76(0.51–1.1) | 0.96(0.72–1.3) | nCRTS-IFI < 40Gy | |
0.62(0.43–0.92)
|
0.70(0.59–0.82)
|
0.70(0.51–0.96)
|
0.88(0.78–0.99)
| 0.92(0.71–1.2) | S-alone |
RT with technique of 3DRT/2DRT | |||||
nCRTS-ENI-3DRT | |||||
0.74(0.46–1.2) | nCRTS-IFI-2DRT | ||||
0.68(0.42–1.1) | 0.92(0.68–1.2) | nCRTS-IFI-3DRT | |||
0.58(0.34–0.99)
| 0.87(0.57–1.3) | 0.94(0.63–1.4) | nCRTS-ENI-2DRT | ||
0.61(0.39–0.94)
| 0.83(0.64–1.1) | 0.90(0.72–1.1) | 0.96(0.66–1.4) | nCTS | |
0.53(0.34–0.80)
|
0.72(0.57–0.88)
|
0.78(0.64–0.94)
| 0.82(0.58–1.2) |
0.86(0.76–0.98)
| S-alone |
Inconsistency assessment and treatment ranking
a. SUCRA values for five outcomes | |||||||||
OS | LR | DM | POM | R0 resection | |||||
Treatment | SUCRA | Treatment | SUCRA | Treatment | SUCRA | Treatment | SUCRA | Treatment | SUCRA |
nCRTS-ENI | 0.93 | nCRTS-IFI | 0.95 | nCRTS-IFI | 0.69 | S alone | 0.83 | S alone | 1.00 |
nCRTS-IFI | 0.71 | nCRTS-ENI | 0.62 | nCRTS-ENI | 0.67 | nCTS | 0.79 | nCTS | 0.67 |
nCTS | 0.36 | nCTS | 0.39 | nCTS | 0.53 | nCRTS-IFI | 0.20 | nCRTS-IFI | 0.19 |
S alone | 0.00 | S alone | 0.04 | S alone | 0.11 | nCRTS-ENI | 0.19 | nCRTS-ENI | 0.15 |
b. SUCRA values of OS for four subgroups | |||||||||
ESCC | EAC | RT dose | RT-technique | ||||||
Treatment | SUCRA | Treatment | SUCRA | Treatment | SUCRA | Treatment | SUCRA | ||
nCRTS-IFI | 0.90 | nCRTS-ENI | 0.96 | nCRTS-ENI- ≥ 40Gy | 0.86 | nCRTS-ENI-3DRT | 0.98 | ||
nCRTS-ENI | 0.68 | nCRTS-IFI | 0.63 | nCRTS-IFI- ≥ 40Gy | 0.75 | nCRTS-IFI-3DRT | 0.69 | ||
nCTS | 0.34 | nCTS | 0.41 | nCRTS-ENI- < 40Gy | 0.73 | nCRTS-IFI-2DRT | 0.54 | ||
S alone | 0.08 | S alone | 0.00 | nCTS | 0.35 | nCRTS-ENI-2DRT | 0.42 | ||
nCRTS-IFI- < 40Gy | 0.25 | nCTS | 0.34 | ||||||
S alone | 0.05 | S alone | 0.03 |