Table 1.
Characteristics of included studies.
| Author | Country | Study type | Cox | Patients (N) | OS HR (95% CI) | Type of cancer | Treatment after resection | Race | Methylation assay method |
|---|---|---|---|---|---|---|---|---|---|
| Arita et al. (31) | Japan | Retrospective | Multivariate | 453 | 0.43 (0.33, 0.56) | GBM | RT + TMZ | Asian | Pyrosequencing |
| Arvold et al. (32) | America | Non-RCT | Univariate | 55 | 0.47 (0.27, 0.81) | GBM | RT + TMZ | Mixed race | NA |
| Azoulay et al. (33) | Canada | Non-RCT | Multivariate | 276 | 0.46 (0.33, 0.64) | GBM | RT + TMZ | Caucasian | NA |
| Brandes et al. (34) | Italy | Non-RCT | Multivariate | 119 | 0.66 (0.47, 0.94) | GBM | RT + TMZ | Caucasian | MSP |
| Brandes et al. (22) | Italy | Non-RCT | Univariate | 25 | 0.19 (0.04, 0.99) | Recurrent GBM | RT + FTM | Caucasian | MSP |
| Chen et al. (35) | China | Non-RCT | Multivariate | 128 | 0.65 (0.41, 1.01) | GBM | RT | Asian | NA |
| Clarke et al. (36) | America | RCT | Univariate | 85 | 0.42 (0.13, 1.39) | GBM | RT + TMZ | Mixed race | MSP |
| Cominelli et al. (37) | Italy | Non-RCT | Univariate | 70 | 0.12 (0.01, 0.98) | GBM | RT + TMZ | Caucasian | MSP |
| Etcheverry et al. (38) | Spain | Non-RCT | Multivariate | 399 | 0.33 (0.24, 0.46) | GBM | RT + TMZ | Caucasian | MSP and Pyrosequencing |
| Gallego Perez-Larraya et al. (39) | France | Non-RCT | Multivariate | 31 | 0.43 (0.20, 0.93) | GBM | TMZ | Caucasian | MSP |
| Gilbert et al. (40) | America | RCT | Univariate | 760 | 0.58 (0.48, 0.69) | GBM | RT + TMZ | Mixed race | MSP |
| Giordano et al. (41) | Germany | Non-RCT | Univariate | 65 | 1.31 (0.75, 2.28) | GBM | RT + TMZ + Celecoxid | Caucasian | NA |
| Glas et al. (42) | Switzerland | Non-RCT | Univariate | 23 | 0.43 (0.22, 0.76) | GBM | RT + TMZ + CCNU | Caucasian | MSP |
| Grossman et al. (43) | America | Non-RCT | Multivariate | 122 | 0.85 (0.56, 1.31) | GBM | RT + TMZ + BCNU | Mixed race | MSP |
| Gutenberg et al. (44) | Germany | Non-RCT | Univariate | 17 | 0.62 (0.43, 0.90) | Recurrent GBM | BCNU + TMZ | Caucasian | MSP |
| Gutenberg et al. (44) | Germany | Non-RCT | Univariate | 13 | 0.99 (0.94, 1.04) | GBM | BCNU | Caucasian | MSP |
| Han et al. (45) | China | Non-RCT | Multivariate | 152 | 0.66 (0.44, 0.98) | GBM | RT + TMZ | Asian | MSP |
| Jungk et al. (46) | Germany | Non-RCT | Multivariate | 63 | 0.89 (0.51, 1.53) | Recurrent GBM | RT + BCNU | Caucasian | MSP |
| Kerkhof et al. (47) | France | Non-RCT | Multivariate | 47 | 1.04 (0.84, 1.29) | GBM | RT + TMZ | Caucasian | NA |
| Kim et al. (48) | Korea | Non-RCT | Multivariate | 70 | 0.30 (0.14, 0.65) | GBM | RT + TMZ | Asian | NA |
| Kim et al. (49) | Korea | Non-RCT | Multivariate | 78 | 0.56 (0.40, 0.83) | GBM | RT + TMZ | Asian | MSP |
| Kreth et al. (50) | Germany | Non-RCT | Multivariate | 222 | 0.30 (0.22, 0.41) | GBM | RT + TMZ | Caucasian | MSP |
| Lai et al. (51) | America | Non-RCT | Multivariate | 70 | 0.49 (0.34, 0.71) | GBM | RT + TMZ + BEV | Mixed race | MSP |
| Lakomy et al. (52) | Czech Republic | Non-RCT | Univariate | 38 | 0.40 (0.21, 0.78) | GBM | RT + TMZ | Caucasian | MS-HRM |
| Lam and Chambers (53) | Canada | Non-RCT | Univariate | 101 | 0.64 (0.38, 1.08) | GBM | RT + TMZ | Caucasian | MSP |
| Lee et al. (54) | Korea | Non-RCT | Multivariate | 36 | 0.22 (0.04, 1.12) | GBM | RT + TMZ | Asian | MSP |
| Liu et al. (21) | China | Non-RCT | Multivariate | 137 | 0.88 (0.58, 1.26) | Recurrent GBM | BEV + FTM | Asian | MSP |
| Lombardi et al. (55) | Italy | Non-RCT | Multivariate | 151 | 0.2 (0.10, 0.50) | GBM | RT + TMZ | Caucasian | MSP |
| Lombardi et al. (56) | Italy | Non-RCT | Univariate | 34 | 0.80 (0.65, 0.97) | Recurrent GBM | TMZ + FTM | Caucasian | MSP |
| Ma et al. (57) | China | Non-RCT | Multivariate | 56 | 0.44 (0.19, 0.83) | GBM | RT + TMZ + ELE | Asian | MSP |
| Malmström et al. (58) | Europe (multicenter) | RCT | Univariate | 72 | 0.56 (0.34, 0.93) | GBM | TMZ | Caucasian | MSP |
| Malmström et al. (58) | Europe (multicenter) | RCT | Univariate | 131 | 0.97 (0.69, 1.38) | GBM | RT | Caucasian | MSP |
| Metellus et al. (59) | France | Non-RCT | Multivariate | 61 | 0.10 (0.02, 0.37) | GBM | RT + TMZ | Caucasian | MSP |
| Metellus et al. (60) | France | Non-RCT | Multivariate | 21 | 0.19 (0.06, 0.77) | Recurrent GBM | TMZ + BCNU | Caucasian | MSP |
| Minniti et al. (61) | Italy | Non-RCT | Multivariate | 243 | 0.30 (0.21, 0.42) | GBM | RT + TMZ | Caucasian | MSP |
| Minniti et al. (62) | Italy | Non-RCT | Multivariate | 83 | 0.41 (0.22, 0.75) | GBM | RT + TMZ | Caucasian | MSP |
| Minniti et al. (63) | Italy | Non-RCT | Multivariate | 36 | 0.40 (0.19, 0.94) | Recurrent GBM | RT + TMZ | Caucasian | MSP |
| Montano et al. (64) | Italy | Non-RCT | Multivariate | 73 | 0.72 (0.37, 1.37) | GBM | RT + TMZ | Caucasian | MSP |
| Motomura et al. (65) | Japan | Non-RCT | Multivariate | 68 | 0.38 (0.18, 0.83) | GBM | RT + TMZ + β-IFN | Asian | Pyrosequencing |
| Murat et al. (66) | Germany | Non-RCT | Multivariate | 42 | 0.06 (0.001, 0.20) | GBM | RT + TMZ | Caucasian | NA |
| Nguyen et al. (67) | America | Non-RCT | Multivariate | 303 | 0.39 (0.30, 0.52) | GBM | RT + TMZ + BEV | Mixed race | MSP |
| Niyazi et al. (68) | Germany | Non-RCT | Univariate | 30 | 0.28 (0.10, 0.77) | GBM | RT + TMZ | Caucasian | MSP |
| Park et al. (69) | Korea | Non-RCT | Multivariate | 48 | 0.81 (0.43, 1.52) | GBM | RT + ACNU + CDDP | Asian | MSP |
| Perry et al. (70) | Canada and Europe | RCT | Univariate | 281 | 0.93 (0.68, 1.21) | GBM | RT | Caucasian | MSP |
| Rosati et al. (71) | Italy | Non-RCT | Multivariate | 47 | 0.27 (0.12, 0.60) | GBM | RT + TMZ | Caucasian | MSP |
| Sana et al. (72) | Czech Republic | Non-RCT | Univariate | 58 | 0.51 (0.29, 0.91) | GBM | RT + TMZ | Caucasian | MS-HRM |
| Saraiva-Esperon et al. (73) | America | Non-RCT | Multivariate | 159 | 0.52 (0.36, 0.73) | GBM | RT + TMZ | Caucasian | MSP |
| Saraiva-Esperon et al. (73) | Australia | Non-RCT | Multivariate | 144 | 0.42 (0.28, 0.63) | GBM | RT + TMZ | Mixed race | Pyrosequencing |
| Schaich et al. (74) | Germany | Non-RCT | Multivariate | 61 | 0.88 (0.36, 2.15) | GBM | RT + TMZ | Caucasian | MSP |
| Schaub et al. (75) | Germany | Non-RCT | Univariate | 143 | 1.13 (0.77, 1.66) | Recurrent GBM | RT + BEV + CPT-11 | Caucasian | NA |
| Shenouda et al. (76) | Canada | Non-RCT | Univariate | 48 | 0.40 (0.19, 0.77) | GBM | RT + TMZ | Caucasian | NA |
| Soffietti et al. (77) | Italy | Non-RCT | Multivariate | 38 | 0.82 (0.38, 1.74) | Recurrent GBM | BEV + FTM | Caucasian | MSP |
| Stummer et al. (78) | Germany | Non-RCT | Univariate | 79 | 0.23 (0.10, 0.52) | GBM | RT + TMZ | Caucasian | MSP |
| Stupp et al. (79) | Europe(multicenter) | Non-RCT | Univariate | 55 | 0.44 (0.21, 0.91) | GBM | RT + TMZ + Cilengitide | Caucasian | MSP |
| Thon et al. (80) | Germany | Non-RCT | Multivariate | 56 | 0.31 (0.16, 0.58) | GBM | RT + TMZ (unresectable) | Caucasian | MSP |
| Vaios et al. (81) | America | Non-RCT | Multivariate | 86 | 0.11 (0.04, 0.26) | GBM | TMZ | Mixed race | NA |
| Van Mieghem et al. (82) | Belgium | Non-RCT | Multivariate | 112 | 0.70 (0.27, 1.8) | GBM | RT + TMZ | Caucasian | MSP |
| Wee et al. (83) | Korea | Non-RCT | Multivariate | 340 | 0.54 (0.41, 0.70) | GBM | RT + TMZ | Asian | MSP |
| Weller et al. (19) | Europe(multicenter) | Non-RCT | Univariate | 105 | 0.55 (0.44, 0.68) | Recurrent GBM | RT + TMZ | Caucasian | MSP |
| Wick et al. (84) | Europe(multicenter) | RCT | Univariate | 101 | 0.96 (0.56, 1.63) | GBM | RT | Caucasian | MSP |
| Wick et al. (84) | Europe(multicenter) | RCT | Univariate | 108 | 0.44 (0.27, 0.72) | GBM | TMZ | Caucasian | MSP |
| Yang et al. (85) | China | Non-RCT | Multivariate | 206 | 0.78 (0.57, 1.04) | GBM | RT + BCNU | Asian | MSP |
| Yang et al. (86) | China | Non-RCT | Multivariate | 238 | 0.59 (0.37, 0.95) | GBM | RT + TMZ | Asian | Pyrosequencing |
| Zhang et al. (87) | China | Non-RCT | Multivariate | 154 | 0.24 (0.15, 0.39) | GBM | RT + TMZ | Asian | NA |
| Author | Country | Study type | Cox | Patients (N) | OS HR (95% CI) | Type of cancer | Treatment after resection | Race | Testing methods |
| Lai et al. (51) | America | Non-RCT | Multivariate | 70 | 0.47 (0.32, 0.70) | GBM | RT + TMZ + BEV | Mixed race | MSP |
| Shenouda et al. (76) | Canada | Non-RCT | Univariate | 48 | 0.47 (0.22, 0.78) | GBM | RT + TMZ | Caucasian | NA |
| Soffietti et al. (77) | Italy | Non-RCT | Multivariate | 38 | 0.48 (0.21, 1.09) | Recurrent GBM | BEV + FTM | Caucasian | MSP |
| Stupp et al. (79) | Europe (multicenter) | Non-RCT | Univariate | 45 | 0.26 (0.13, 0.51) | GBM | RT + TMZ + Cilengitide | Caucasian | MSP |
| Arita et al. (31) | Japan | Non-RCT | Multivariate | 453 | 0.48 (0.37, 0.61) | GBM | RT + TMZ | Asian | Pyrosequencing |
| Lee et al. (54) | Korea | Non-RCT | Multivariate | 36 | 0.40 (0.15, 1.1) | GBM | RT + TMZ | Asian | MSP |
| Metellus et al. (59) | France | Non-RCT | Multivariate | 61 | 0.42 (0.21, 0.92) | GBM | RT + TMZ | Caucasian | MSP |
| Metellus et al. (60) | France | Non-RCT | Multivariate | 21 | 0.15 (0.08, 0.48) | Recurrent GBM | TMZ + BCNU | Caucasian | MSP |
| Minniti et al. (61) | Italy | Non-RCT | Multivariate | 243 | 0.29 (0.21, 0.40) | GBM | RT + TMZ | Caucasian | MSP |
| Minniti et al. (63) | Italy | Non-RCT | Multivariate | 36 | 0.38 (0.18, 0.79) | Recurrent GBM | RT + TMZ | Caucasian | MSP |
| Ohno et al. (88) | Japan | Non-RCT | Multivariate | 88 | 0.35 (0.21, 0.59) | GBM | RT + TMZ + ACNU | Asian | Pyrosequencing |
| Thon et al. (80) | Germany | Non-RCT | Multivariate | 56 | 0.32 (0.17, 0.59) | GBM | RT + TMZ | Caucasian | MSP |
| Weller et al. (19) | Europe (multicenter) | Non-RCT | Univariate | 105 | 0.57 (0.35, 0.90) | Recurrent GBM | RT + TMZ | Caucasian | MSP |
| Gilbert et al. (40) | America | RCT | Univariate | 760 | 0.61 (0.52, 0.73) | GBM | RT + TMZ | Mixed race | MSP |
| Cominelli et al. (37) | Italy | Non-RCT | Univariate | 70 | 0.29 (0.04, 2.24) | GBM | RT + TMZ | Caucasian | MSP |
| Giordano et al. (41) | Germany | Non-RCT | Univariate | 65 | 2.04 (1.04, 4.00) | GBM | RT + TMZ | Caucasian | NA |
| Gutenberg et al. (44) | Germany | Non-RCT | Univariate | 13 | 0.93 (0.70, 1.24) | GBM | BCNU | Caucasian | MSP |
| Gutenberg et al. (44) | Germany | Non-RCT | Univariate | 17 | 0.60 (0.33, 1.07) | Recurrent GBM | BCNU + TMZ | Caucasian | MSP |
| Kim et al. (89) | Korea | Non-RCT | Multivariate | 72 | 0.47 (0.27, 0.82) | Recurrent GBM | RT + TMZ | Asian | MSP |
| Kim et al. (49) | Korea | Non-RCT | Multivariate | 78 | 0.63 (0.46, 0.91) | GBM | RT + TMZ | Asian | MSP |
| Lakomy et al. (52) | Czech Republic | Non-RCT | Univariate | 38 | 0.48 (0.25, 0.92) | GBM | RT + TMZ | Caucasian | MS-HRM |
| Liu et al. (21) | China | Non-RCT | Multivariate | 137 | 0.69 (0.52, 0.97) | Recurrent GBM | BEV + FTM | Asian | MSP |
| Lombardi et al. (56) | Italy | Non-RCT | Univariate | 34 | 0.72 (0.59, 0.87) | Recurrent GBM | TMZ + FTM | Caucasian | MSP |
| Nguyen et al. (67) | America | Non-RCT | Multivariate | 303 | 0.43 (0.33, 0.57) | GBM | RT + TMZ + BEV | Mixed race | MSP |
| Sana et al. (72) | Czech Republic | Non-RCT | Univariate | 58 | 0.54 (0.23, 0.96) | GBM | RT + TMZ | Caucasian | MS-HRM |
Studies enrolled for OS analysis. TMZ, temozolomide; RCT, randomized control trial; RT, radiotherapy; BCNU, carmustine; FTM; fotemustine; BEV, bevacizumab; CCNU, lomustine; ELE, β-element; ACNU, nimustine; CDDP, cisplatin; β-IFN, interferon-β; CPT-11, irinotecan; MSP, methylation-specific PCR; NA, not available.
Studies enrolled for PFS analysis. TMZ, temozolomide; RCT, randomized control trial. RT, radiotherapy; BCNU, carmustine; FTM; fotemustine; BEV, bevacizumab; ACNU, nimustine; MSP, methylation-specific PCR; NA, not available.