Table 1. Description of trials included in the meta-analysis.
| First author, Year, (reference) | Race(Region) | Clinical stage (TNM classification) | Histology(WHO classification) | Radiotherapy | Concurrent chemoradiotherapy | Induction chemotherapy | Adjuvant chemotherapy | Patients randomized (treatment/control) | Median follow-up(month) |
|---|---|---|---|---|---|---|---|---|---|
| Fountzilas et al.,2012, [9] | Greek(Greece) | AJCC/UICC 6th edition IIB-IVB | 1-3 | (79 patients) 3D-CRT and (62 patients) 2D-CRT: 2.0Gy/F×5F/wk; primary site 66-70 Gy; positive nodes 66-70 Gy; pharyngeal extension and residual nodes 50 Gy. | Cisplatin 40 mg/m2 d1, q1wk×8 | Cisplatin 75 mg/m2 d1; Epirubicin 75 mg/m2 d1; Paclitaxel 175 mg/m2 d1; q3wks×3 | 72/69 | 55 (0.5 – 76.2) | |
| Tan et al. 2015, [18] | Singaporean(Singapore) | UICC/AJCC 5th edition T3-4NxM0 or TxN2-3M0 | 2,3 | (168 patients) IMRT: GTVnx: 69.96Gy/2.12Gy/33F; GTVnd: 69.96Gy/2.12Gy/33F; CTV1: 60Gy/1.82Gy/33F. (4 patients) 2D-CRT: primary site 70Gy/2Gy/35F; positive nodes 70Gy/2Gy/35F; pharyngeal extension and residual nodes 60Gy/2Gy/30F. | Cisplatin 40 mg/m2 d1, q1wk×8 | Paclitaxel 70mg/m2 d1, d8; Carboplatin AUC=2.5 d1, d8; Gemcitabine 1000mg/m2 d1, d8; q3wks×3 | 86/86 | 40.8(13.2 - 100.8) | |
| Ma et al. 2014, [14] | Chinese(Mainland China) | UICC/AJCC 7th edition III-IVB (except T3-4N0) | 2,3 | IMRT (radical radiotherapy) | Cisplatin 100 mg/m2 d1, q3wks×3 | Docetaxel 60mg/m2 d1; Cisplatin 60mg/m2 d1; Fluorouracil 600 mg/m2 d1-5; q3wks×3 | 241/239 | 18.6 (0.8 - 34) | |
| Hui et al. 2009, [19] | Chinese(Hong Kong) | UICC/AJCC 5th edition III-IVB | NR | (17 patients) IMRT and (48 patients) 2D-CRT: 2 Gy/F×5F/wk; total 66 Gy; residual boost of 7.5 Gy. | Cisplatin 40 mg/m2 d1, q1wk×8 | Docetaxel 75 mg/m2 d1; Cisplatin 75 mg/m2 d1; q3wk×2 | 34/31 | 51.6 | |
| Huang et al. 2012, [17] | Chinese Mainland (China) | AJCC/UICC 6th edition III-IVB | 2,3 | 2D-CRT: 2.0Gy/F×5F/wk; primary site 65-78 Gy; positive nodes 60-70 Gy; pharyngeal extension and residual nodes 50-54 Gy. | Caboplatin AUC = 6 d7, d28, d49 | Caboplatin AUC=6 d1; Fluorouracil 750mg/m2, d1-5; q3wks×2 | 100/100 | 46.8 | |
| Gao et al. 2013, [15] | Chinese(Mainland China) | 1992 Fuzhou stage T3-4N2-3M0 | 2,3 | 2D-CRT: 2.0Gy/F×5F/wk; primary site 70-74 Gy; positive nodes 66-70 Gy; pharyngeal extension and residual nodes 50 Gy. | Cisplatin 40 mg/m2 d1, q1wk×7 | Cisplatin 30mg/m2 d1-3; Fluorouracil 450mg/m2 d1-3; q3wks×2 | 57/55 | 42 (> 24) | |
| Sun, 2009, [16]a | Chinese(Mainland China) | 1992 Fuzhou stage III-IVA | 2,3 | (156 patients) IMRT: 5F/wk; GTVnx: 68Gy/30F; GTVnd: 60 - 66Gy/30F; CTVl: 60Gy/30F; CTV2: 54Gy/30F. (57 patients) 2D-CRT: 2.0Gy/F×5F/wk; primary site 70 Gy; positive nodes 66-70 Gy; pharyngeal extension and residual nodes 50 Gy. | Cisplatin 80mg/m2 d1, q3wks×2 | Group 1 (76 patients): Cisplatin 80mg/m2 d1; Fluorouracil 1.5g/m2 d1-2; q3wks×2 Group 2 (66 patients) : Fluorouracil 1.5g/m2 d1-2; Carboplatin AUC = 6; q3wks×2 | 142/71 | 26.3 (2.5 - 44.7) | |
| Lee et al, 2015, [13]b | Chinese(Hong Kong and Mainland China) | AJCC/UICC 6th edition III-IVB | 2,3 | IMRTc 2.0Gy/F×5F/wk or 2.0Gy/F×6F/wk; gross tumor target 70 Gy; positive nodes <70 Gy; pharyngeal extension and residual nodes 50 Gy. | Cisplatin 100 mg/m2 d1, q3wks×2/3 | Cisplatin 100 mg/m2 d1, Fluorouracil 1g/ m2 d1-5, q3wks×2/3; or Cisplatin 100 mg/m2 d1, capecitabine 2g/ m2 d1-14, q3wks×2/3 | Cisplatin 80 mg/m2 d1, Fluorouracil 1g/ m2 d1-4, q4wks×3 | 538/264 | 39.6(1.2-85.2) |
| Ruste et al, 2011, [20] | Philippinese(Philippines) | III-IVB | 2,3 | 2D-CRT: 2.0Gy/F×5F/wk; primary site 70Gy, N0 disease 50Gy, nodes<2cm 66 Gy, nodes greater than 2cm 70Gy. | Cisplatin 25 mg/m2 d1-4, q3wks×3 | Cisplatin 20 mg/m2 d1-4, q4wks×3; 5-Fluorouracil 1000 mg/m2 d1-4; q4wks×3 | Cisplatin 20 mg/m2 d1-4; 5-Fluorouracil 1000 mg/m2 d1-4; q4wks×3 | 14/16 | 19(8-30) |
Patients were allocated to 6 arms: arm 1A (conventional fractionation radiotherapy, adjuvant chemotherapy using Cisplatin plus 5-Fluorouracil ), arm 2A (conventional fractionation radiotherapy, neoadjuvant chemotherapy using Cisplatin plus 5-Fluorouracil), arm 3A (conventional fractionation radiotherapy, neoadjuvant chemotherapy using Cisplatin plus Capecitabine), arm 1B (accelerated fractionation radiotherapy, adjuvant chemotherapy using Cisplatin plus 5-Fluorouracil), arm 2B (accelerated fractionation radiotherapy, neoadjuvant chemotherapy using Cisplatin plus 5-Fluorouracil), arm 3B (accelerated fractionation radiotherapy, neoadjuvant chemotherapy using Cisplatin plus Capecitabine). In this meta-analysis, we combined arm 2A, arm 3A, arm 2B, and arm 3B together as a treatment group, and combined arm 1A and arm 1B together as a control group.
Patients were divided into three study groups, comparing concurrent chemoradiotherapy (control group) with two different NACT plus CCRT treatments (treatment group). For the purpose of the present meta-analysis, the control group was directly used, and the two treatment groups were pooled together.
2D-CRT, Two-dimensional conformal radiation therapy; 3D-CRT, Three-dimensional conformal radiation therapy; AJCC, American Joint Committee on Cancer; AUC, area under the curve; CTV, clinical target volume; F, fraction; GTV, Gross tumor volume; IMRT, intensity-modulated radiotherapy; TNM, Tumour Nodes Metastasis; UICC, International Union Against Cancer; WHO, World Health Organization; d, day; q1wk, every 1 week; q3wk, every 3 weeks; wk, week.
95% patients were treated with IMRT.