Background
Methods
Data sources and search strategy
Inclusion criteria
Data extraction
Index tests and reference standard
Methodological quality assessment
Data analysis plan
Clinical Settings (study numbers) [analysis model] | Mean Sen & (95% CI) | Mean Spe & (95% CI) | Mean DOR & (95% CI) | Mean LR + & (95% CI) | Mean LR- & (95% CI) | AUC & (95% CI) |
---|---|---|---|---|---|---|
EOC (n = 6) [bi]
| 0.89 (0.84-0.93) | 0.83 (0.77-0.88) | 41.43 (26.17-65.57) | 5.25 (3.85-7.16) | 0.13 (0.08-0.20) | 0.93 (0.90-0.95)=
|
[I2 =71.6%] | [I2 =80.7%] | [I2 =44.2%] | [I2 =75.7%] | [I2 =71.6%] | ||
EOC- preM (n = 5) [bi]
| 0.82 (0.67-0.91) | 0.82 (0.74-0.88) | 20.55 (9.70-43.53) | 4.50 (3.19-6.36) | 0.22 (0.12-0.42) | 0.88 (0.85-0.91) ●
|
[I2 =60.1%] | [I2 =74.8%] | [I2 =43.3%] | [I2 =66.0%] | [I2 =62.5%] | ||
EOC- postM (n = 5) [bi]
| 0.93 (0.89-0.96) ▴
| 0.79 (0.73-0.83) | 47.27 (27.34-81.73) | 4.33 (3.41-5.50) | 0.09 (0.06-0.15) | 0.89 (0.86-0.92) ●
|
[I2 =51.6%] | [I2 =16.2%] | [I2 =0.0%] | [I2 =15.6%] | [I2 =45.8%] | ||
EOC- early stage (n = 3) [uni]
| 0.81 (0.71-0.89) ●=
| 0.76 (0.73-0.79) ●
| 17.18 (9.08-32.50) =
| 3.67 (2.56-5.28) | 0.24 (0.15-0.38) | 0.88 (0.83-0.93)=
|
[I2 =0.0%] | [I2 =68.2%] | [I2 =0.0%] | [I2 =63.4%] | [I2 =0.0%] | ||
EOC- advanced stage (n = 3) [uni]
| 0.98 (0.94-1.00) ●
| 0.76 (0.73-0.79) ●
| 149.08 (47.80-464.95) | 4.17 (3.37-5.17) | 0.04 (0.01-0.13) | 0.97 (0.95-1.00) |
[I2 =49.8%] | [I2 =68.2%] | [I2 =0.0%] | [I2 =55.0%] | [I2 =28.1%] | ||
EOC- methods High concern (n = 3) [uni]
| 0.90 (0.85-0.93) | 0.87 (0.83-0.90) ★●
| 62.84 (3.25-112.04) | 7.29(4.33-12.26) | 0.12 (0.08-0.18) | 0.95 (0.93-0.97) |
[I2 =0.0%] | [I2 =67.5%] | [I2 =0.0%] | [I2 =58.4%] | [I2 =0.0%] | ||
EOC- methods Low concern (n = 3) [uni]
| 0.89 (0.85-0.93) | 0.75 (0.72-0.78) ●
| 29.57 (12.85-68.03) | 3.74 (3.29-4.25) | 0.14 (0.04-0.44) | 0.91 (0.86-0.96) |
[I2 =85.5%] | [I2 =0.0%] | [I2 =56.8%] | [I2 =0.0%] | [I2 =88.2%] | ||
EOC (LMP/BL) (n = 3) [uni]
| 0.88 (0.84-0.92) | 0.77 (0.74-0.80) | 33.36 (15.02-74.06) | 4.37 (2.88-6.64) | 0.15 (0.11-0.20) | 0.92 (0.88-0.96) |
[I2 =0.0%] | [I2 =89.3%] | [I2 =66.8%] | [I2 =84.6%] | [I2 =0.0%] | ||
OC (n = 3) [uni]
| 0.86 (0.82-0.89) | 0.78 (0.75-0.81) | 21. 436 (15.28-30.08) | 4.11 (3.14-5.38) | 0.19 (0.14-0.23) | 0.89 (0.87-0.92)●
|
[I2 =0.0%] | [I2 =68.9%] | [I2 =0.0%] | [I2 =61.8%] | [I2 =0.0%] |
Results
Search results
Reference | Country | Study Design | Subjects (number) | Menopausal Condition PreM/PostM | Index Tests (Methods) | Cut-off Value | Proven cancer N (%) |
---|---|---|---|---|---|---|---|
Abdel-Azeez et al., 2010
| Egypt | Cross-section | 65 | 18/47 | HE4 (EIA); CA125 (ECLIA) | HE4: 72pM; CA125: 35U/mL | OC: 41 (63.1%) |
Bandiera et al., 2011
| Italy | Cross-section | 419 | 134/284 (1 patient with unknown stage was not analyzed) | ROMA | ROMA: preM 7.4% postM 25.3%; | EOC: 114 (27.2%) |
HE4 (CMIA); | HE4: preM 70pM, postM 140pM; | ||||||
CA125 (CMIA) | CA125: 35U/mL | ||||||
Chang et al., 2011
| China | Cross-section | 118 | - | HE4 (EIA); CA125 (EIA) | HE4: 150pM; CA125: 35U/mL | OC: 52 (44.1%) |
Holcomb et al., 2011
| USA | Cross-section | 229 | 229/- | HE4 (CMIA); CA125 (CMIA) | HE4: 70pM; CA125: 35U/mL | EOC: 18 (7.86%) |
Jacob et al., 2011
| Switzerland | Cross-section | 160 | 84/76 | ROMA | ROMA: 13.1% | EOC: 29 (18.1%) |
HE4 (ELISA); CA125 (ELISA) | HE4: 70pM; CA125: 35U/mL | OC: 56 (35%) | |||||
Kim et al., 2011
| Korea | Cross-section | 159 | 51/108 | ROMA | ROMA: preM 7.6% postM 10.9%; | EOC: 72 (45.3%) |
HE4 (CMIA); CA125 (CMIA) | HE4: 70pM; CA125: 35 IU/mL | OC: 78 (49.1%) | |||||
Montagnana et al., 2011
| Italy | Cross-section | 104 | 51/53 | ROMA | ROMA: preM12.5% postM14.4%; | EOC: 55 (52.9%) |
HE4 (EIA); CA125 (CLEIA) | HE4: 74.2pM; CA125: 35U/mL | ||||||
Moore et al., 2008
| USA | Cross-section | 233 | - | HE4 (EIA); CA125 (RIA) | - | EOC: 67 (28.8%) |
Moore et al., 2009
| USA | Cross-section | 531 | 248/283 | ROMA | ROMA: preM 13.1% postM 27.7% | EOC: 129 (26.8%) |
HE4 (EIA); CA125 (CMIA) | OC: 154 (29.0%) | ||||||
Moore et al., 2011
| USA | Cross-section | 472 | 255/217 | ROMA | ROMA: preM 13.1%; postM 27.7% | EOC: 48 (10.2%) |
HE4 (ELISA); CA125 (CMIA) | |||||||
Van Gorp et al., 2011
| Belgium | Cross-section | 389 | 184/205 | ROMA | ROMA: preM 12.5% postM 14.4%; | OC: 161 (41.4%) |
HE4 (EIA); CA125 (EIA) | HE4: 70pM;CA125: 35U/mL |
Methods of index tests
Methodological quality of all included studies
Study ID | Risk of Bias | Concerns Regarding Applicability | |||||||
---|---|---|---|---|---|---|---|---|---|
PATIENT SELECTION | INDEX TEST | REFERENCE STANDARD | FLOW & TIMING | PATIENT SELECTION | INDEX TEST | REFERENCE STANDARD | |||
HE4 | CA125 | ROMA | |||||||
Abdel-Azeez et al., 2010 | ? | ? | ? | ? | ☺ | ☺ | ☺ | - | ☺ |
Bandiera et al., 2011 | ☻ | ? | ? | ☻ | ☻ | ☻ | ☺ | ☻ | ☺ |
Chang et al., 2011 | ? | ☺ | ☺ | ? | ☺ | ☺ | ☻ | - | ? |
Holcomb et al., 2011 | ☻ | ☺ | ☺ | ☻ | ? | ☻ | ☺ | - | ☺ |
Jacob et al., 2011 | ? | ☺ | ☺ | ☻ | ? | ☺ | ☻ | ☻ | ☺ |
Kim et al., 2011 | ☺ | ☺ | ☺ | ☺ | ☺ | ☻ | ☺ | ☻ | ☺ |
Montagnana et al., 2011 | ☺ | ? | ☺ | ☺ | ☺ | ☺ | ☺ | ☺ | ☺ |
Moore et al., 2008 | ? | ☻ | ☺ | ☺ | ☺ | ☺ | ☻ | - | ☺ |
Moore et al. 2009 | ☺ | ? | ☺ | ☻ | ☺ | ☺ | ☺ | ☺ | ☺ |
Moore et al., 2011 | ? | ☺ | ☺ | ☻ | ☺ | ☺ | ☺ | ☺ | ☺ |
Van Gorp et al. 2011 | ☺ | ☺ | ☺ | ☺ | ☺ | ☺ | ☻ | ☻ | ☺ |
Performance of ROMA for predicting EOC
Performance comparison between HE4 and CA125
Settings (study numbers) [analysis model] | Mean Sen (95% CI) | Mean Spe (95% CI) | Mean DOR (95% CI) | Mean LR+ (95% CI) | Mean LR- (95% CI) | AUC (95% CI) | |
---|---|---|---|---|---|---|---|
EOC
|
EOC- HE4 (n = 4) [bi]
| 0.79 (0.74-0.84) | 0.93 (0.87-0.96) | 47.59 (23.87-94.90) | 10.64 (5.93-19.10) | 0.22 (0.17-0.29) | 0.82 (0.78-0.85) #
|
[I2 =0.0%] |
# [I2 =72.0%] | [I2 =41.3%] | [I2 =71.3%] | [I2 =0.0%] | |||
EOC-CA125 (n = 4) [bi]
| 0.77 (0.58-0.89) | 0.84 (0.76-0.90) | 18.86 (10.22-31.21) | 4.90 (3.63-6.61) | 0.27 (0.15-0.50) | 0.88 (0.85-0.91) | |
[I2 =90.2%] | [I2 =85.3%] | [I2 =57.4%] | [I2 =56.2%] | [I2 =85.2%] | |||
OC
|
OC-HE4 (n = 5) [bi]
| 0.77(0.72-0.81) | 0.89 (0.82-0.93) | 25.37 (14.58-44.14) | 6.66 (4.25-10.43) | 0.26 (0.22-0.32) | 0.79 (0.76-0.83) #
|
[I2 =0.0%] | [I2 =58.9%] | [I2 =40.7%] | [I2 =50.3%] | [I2 = 0.0%] | |||
OC-CA125 (n = 5) [bi]
| 0.73 (0.63-0.81) | 0.86 (0.81-0.90) | 17.12 (11.64-25.19) | 5.35 (4.09-7.00) | 0.31 (0.23-0.43) | 0.89 (0.85-0.91) | |
[I2 =80.3%] | [I2 =49.4%] | [I2 =7.8%] | [I2 =0.0%] | [I2 =75.2%] |
Performance comparison among ROMA, HE4 and CA125 for EOC prediction
Settings (study numbers) [analysis model] | Mean Sen (95% CI) | Mean Spe (95% CI) | Mean DOR (95% CI) | Mean LR+ (95% CI) | Mean LR- (95% CI) | AUC (95% CI) |
---|---|---|---|---|---|---|
EOC- ROMA | 0.86 (0.81-0.91)* | 0.84 (0.79-0.88) *#
| 32.72 (12.42-86.21) | 5.35 (4.09-7.01) | 0.17 (0.07-0.40) | 0.92 (0.86-0.97) |
(n = 3) [uni] | [I2 =75.5%] | [I2 =0.0%] | [I2 =64.4%] | [I2 =0.0%] | [I2 =80.5%] | |
EOC-HE4 | 0.80 (0.73-0.85) | 0.94 (0.90-0.96) | 67.99 (31.97-144.60) | 12.21 (4.25-35.11) | 0.22 (0.17-0.29) | 0.95 (0.92-0.98) |
(n = 3) [uni] | [I2 =0.0%] | [I2 =78.2%] | [I2 =19.2%] | [I2 =79.0%] | [I2 =0.0%] | |
EOC-CA125 | 0.84 (0.78-0.89) | 0.78 (0.73-0.83) * | 19.15 (7.26-50.53) | 3.81 (2.66-5.46) | 0.23 (0.09-0.58) | 0.88 (0.81-0.96) |
(n = 3) [uni] | [I2 =90.0%] | [I2 =79.6%] | [I2 =68.8%] | [I2 =41.4%] | [I2 =87.6%] |