Table 1.
The baseline characteristics and study quality of included studies.
| Study | Country and year | Study design | No. of patients (M/F) | Arm | Age mean ± SD/median (range) | Follow-up mean ± SD/median (range) | T category (0-2/3/4/NR) | N category (N-/N+/NR) | TNM stage (0-I/II/III/IV/NR) | Type of neoadjuvant chemotherapy | Type of adjuvant chemotherapy | NOS |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Javier Sastre | Spain 2016 | nRCT | 87 | OX | 69 (35-86) | NR | ypT3-4: 50 | yp: -/50/- | NR | 5.4 Gy boost + 45 Gy/25F, CAP+5-FU or UTF | FOLFOX or XELOX | 7 |
| (50/37) | FL | NR | ypT0-2: 37 | yp: 37/-/- | NR | CAP or 5 − FU + LV or raltitrexed | ||||||
| Rodel | German 2015 | RCT | 1236 | OX | Median: 64 | 50 (38–61) m | yp: 316/260/17/3 | yp: 416/175/5 | yp:252/154/154/20/16 | 50.4Gy/28F, FU+ oxaliplatin | FU + LV+ oxaliplatin | 7 |
| (874/362) | FL | Median: 63 | yp: 310/278/26/1 | yp: 423/191/1 | yp:257/148/169/35/6 | 50.4 Gy/28F, FU | FU | |||||
| Hong, Y. S. | Korea | RCT | 321 | OX | 54 (25-79) | 74.1 (56.2-88.0) m | yp: 24/133/3/- | yp: 58/102/- | yp: -/58/102/-/- | 50Gy, FU ± LV or CAP or tegafur/uracil | FU + LV+ oxaliplatin | 8 |
| 2019 | (234/87) | FL | 55 (27-81) | yp: 24/131/6/- | yp: 65/96/- | yp: -/65/96/-/- | FU + LV | |||||
| Chung, M. J.∗ | Korea | nRCT | 1442 | OX | NR | ypT0-2: 10, ypT3-4: 58 | yp: 13/55/- | NR | 45 Gy/25F + 5.4 Gy/3F, 5 − FU + LV + CAP | 5 − FU + LV + oxaliplatin | 8 | |
| 2019 | (975/467) | FL | NR | 48.8 (6.5-141.0) m | ypT0-2: 37, ypT3-4: 167 | yp: 37/167/- | NR | 5 − FU + LV | ||||
| OB | NR | ypT0-2: 96, ypT3-4: 85 | yp: 133/48/- | NR | / | |||||||
| Loree, J. M. | Canada | nRCT | 485 | OX | 61 (52-68) | Median: 5.1y | NR | NR | c: 5/136/201/-/15 | 45 to 54 Gy, 5-FU or CAP or FOLFOX or IXO | FOLFOX or CAPOX | 7 |
| 2018 | (343/142) | FL | Median: 3.64y | NR | NR | 5-FU or CAP | ||||||
| OB | 64 (56-72) | Median: 4.4y | NR | NR | c: 3/44/72/-/9 | / | ||||||
| Garlipp, B. | German | nRCT | 1497 | OX | 65 (29.0–88.0) | yp: 71/82/7/- | yp: 86/74/- | NR | Oxaliplatin +5-FU or FA or CAP | 8 | ||
| 2016 | (1006/490) | FL | 67 (26.0–85.0) | Median: 38 m | yp: 356/383/29/- | yp: 522/246/- | NR | 5FU-only-based CRT | 5-FU or FA or CAP | |||
| OB | 68.5 (23.0–89.0) | yp: 283/268/17/1 | yp: 435/134/- | NR | / | |||||||
| Peng, J. H. | China | nRCT | 105 | CT | 51.3 ± 11.4 | 49 (4–89) m | c: 4/54/25/- | c: 27/56/- | c: -/27/56/-/- | 46–50Gy, XELOX | XELOX | 7 |
| 2018 | (70/35) | OB | 58.9 ± 11.6 | c: 0/14/8/- | c: 8/14/- | c: -/8/14/-/- | / | |||||
| Glynne-Jones, R. | UK | RCT | 113 | CT | 59.0 (55.0–66.0) | Median: 44.8 m | yp: 25/27/2/- | yp: 44/10/- | NR | 5FU-based CRT | XELOX | 5 |
| 2014 | (30/83) | OB | 58.0 (52.0–65.0) | Median: 44.8 m | yp: 17/38/4/- | yp: 31/28/- | NR | / | ||||
| You, K. Y. | China | nRCT | 160 | CT | 54 (15–80) | Median: 47 m | yp: 65/37/10/3 | c: 41/74/- | c: -/41/74/-/- | 46Gy/23F, FOLFOX-6 or XELOX | FOLFOX or XELOX or CAP | 6 |
| 2014 | (119/41) | OB | 62 (39–77) | Median: 41 m | yp: 26/16/3/- | c: 20/25/- | c: -/20/25/-/- | / | ||||
| Sun, Z. | USA | nRCT | 12696 | CT | 56.0 (48–64) | NR | NR | NR | yp: -/1586/2437/-/- | Chemoradiation | NR | 6 |
| 2017 | (7853/4843) | OB | 60.0 (51–69) | NR | NR | NR | yp: -/4401/4272/-/- | NR | ||||
| Sainato, A. | Italy 2014 | RCT | 634 (421/213) | CT | Mean: 60.5 | Median: 63.7 m | ypT0-2: 150, ypT3-4: 143, ypTx: 3 | c: 168/112/44 | NR | 45 Gy/28F, 5-FU + FA | 5-FU + FA | 8 |
| OB | Mean: 60.6 | Median: 63.7 m | ypT0-2: 169, ypT3-4: 120, ypTx: 5 | c: 194/76/40 | NR | / | ||||||
| Kulaylat, A. S. | USA | nRCT | 8344 | CT | NR | NR | NR | yp: 2645/1527/- | c: -/1823/2349/-/- | Chemoradiation | NR | 7 |
| 2017 | (5212/3132) | OB | NR | NR | NR | yp: 3063/1109/- | c: -/1869/2303/-/- | NR | ||||
| Kuan, F. C. | China | nRCT | 259 | CT | 56.67 ± 13.04 | 38 (26-56) w | c: 11/93/9/1 | c: 33/81/- | c: -/33/81/-/- | 40-60Gy, 5-FU/LV, tegafur or CAP | NR | 6 |
| 2017 | (164/95) | OB | 61.88 ± 11.31 | 36 (23-56) w | c: 21/114/10/- | c: 52/91/2 | c: -/54/91/-/- | NR | ||||
| Kiran, R. P. | USA | nRCT | 128 | CT | 55.6 ± 11.8 | 51.2 (25.8–68.1) m | yp: 29/28/1/- | NR | yp: 28/30/-/-/- | 50.4 Gy, 5-FU or 5 − FU + LV | NR | 8 |
| 2012 | (90/38) | OB | 59.4 ± 12.1 | 54.1 (34.7–78.2) m | yp: 51/19/0/- | NR | yp: 48/22/-/-/- | NR | ||||
| Jung, K. U. | Korea | nRCT | 476 | CT | 54.0 (46.5-62.5) | Median: 48.4 m | yp: 217/206/18/- | yp: 301/140/- | yp: 182/118/141/-/- | 44 Gy/22F, 5-FU or Xeloda or FU + LV | 5-FU | 8 |
| 2015 | (312/164) | OB | 64.0 (47.0–72.0) | Median: 42.1 m | yp: 17/17/1/- | yp: 23/12/- | yp: 17/6/12/-/- | / | ||||
| Geva, R. | Israel | nRCT | 52 | CT | 60.9 ± 11.9 | 68.4 ± 43.4 m | c: 1/31/-/3 | c: 23/9/3 | NR | 45 or 50.4Gy, 5-FU or CAP | NR | 8 |
| 2014 | (32/20) | OB | 68.7 ± 10.8 | 49.4 ± 38.9 m | c: 2/14/-/1 | c: 12/3/2 | NR | 50.4Gy, 5-FU or CAP | NR | |||
| Breugom, A. J. | Netherlands | RCT | 437 (270/167) | CT | Median: 61.13 ± 8.94 | 5.0 (0.02–13.12) y | NR | NR | yp: -/39/177/-/- | 25Gy/5F or 45–50 Gy/25F, 5-FU | 5-FU or LV | 8 |
| 2015 | OB | Median: 61.08 ± 9.13 | NR | NR | yp: -/32/189/-/- | / | ||||||
| Bosset, J. F. | France | RCT | 1011 | CT | NR | 10·4 (7·8–13·1) y | c: -/454/52/- | ypN+: 140 | NR | 45 Gy/25F; 45 Gy/25F, FU + LV | FU + LV | 8 |
| 2014 | (739/272) | OB | NR | c: -/456/49/- | ypN+: 154 | NR | / | |||||
| Ahn, D. H. | USA | nRCT | 110 | CT | 54.3 (27-76) | NR | yp: 68/-/-/3 | p: 37/28/6 | NR | Chemoradiation | 5-FU or CAP or FOLFOX | 5 |
| 2017 | (68/42) | OB | 62 (21-79) | NR | yp: 38/-/-/1 | p: 29/7/3 | NR | / | ||||
| Hofheinz, R. D. | German | RCT | 1069 | OX | NR | Median: 31 m | NR | NR | NR | 45-50.4 Gy, CAP + OX | CAP + OX | 6 |
| 2017 | FL | NR | Median: 31 m | NR | NR | NR | 45-50.4 Gy, CAP | CAP |
∗Patient characteristics based on T category and N category were after propensity-score matching. RCT: randomized controlled trial; nRCT: nonrandomized controlled trial; M/F: male/female; OX: oxaliplatin-based group; FL: fluorouracil-based group; OB: observation group; CT: chemotherapy group; m: month; y: year; w: week; c: clinical stage; yp: pathologic stage after receiving neoadjuvant chemotherapy; p: pathologic stage; FU: fluorouracil; UTF: uracil + tegafur + fluorouracil; LV: leucovorin; CAP: capecitabine; FA: folinic acid; FOLFOX: fluorouracil + leucovorin + oxaliplatin; XELOX: capecitabine + oxaliplatin; CAPOX: capecitabine + oxaliplatin; IXO: irinotecan + capecitabine + oxaliplatin; “/”: there is no relevant data; NR: not reported; NOS: Newcastle–Ottawa Scale criteria.