Table 2. Overall Prevalence of BRAF Mutations in mCRC and Subgroups.
| N studiesc | Summary prevalence (95% CI) | P-Het; I2 | P value for heterogeneity within subgroups | |
|---|---|---|---|---|
| Overall | 142 | 7.1% (6.5% - 7.8%) | < 0.001; 66.3% | |
| Exon 15a | 44 | 7.0% (6.1% - 8.1%) | 0.001; 45.8% | |
| Val600Glu (V600E) | 75 | 6.8% (5.8% - 7.9%) | < 0.001; 76.9% | 0.002 |
| Asp594Gly | 4 | 0.6% (0.1% - 2.8%) | 0.064; 58.8% | |
| Sex | ||||
| Male | 12 | 7.9% (6.5% - 9.7%) | 0.076; 39.7% | 0.018 |
| Female | 12 | 11.0% (9.2% - 13.1%) | 0.260; 18.7% | |
| Median age of study population | ||||
| < 62 | 35 | 7.8% (6.6% - 9.1%) | < 0.001; 55.5% | 0.970 |
| ≥ 62 | 57 | 7.8% (6.7% - 9.1%) | < 0.001; 68.6% | |
| Meta-regression on median age | 92 | 0.012 (-0.014 - 0.036) | N/A | 0.390 |
| Race | ||||
| < 88% White/Caucasian | 7 | 7.1% (5.5% - 9.2%) | 0.915; 0.0% | 0.855 |
| ≥ 88% White/Caucasian | 5 | 7.6% (4.1% - 13.7%) | 0.007; 71.7% | |
| Study location | ||||
| Asia | 29 | 6.0% (5.1% - 7.0%) | 0.175; 19.6% | 0.002 |
| Australia | 7 | 11.1% (8.6% - 14.2%) | 0.062; 49.9% | |
| Europe | 79 | 7.2% (6.3% - 8.1%) | < 0.001; 68.2% | |
| Multi-country | 8 | 8.3% (5.4% - 12.5%) | < 0.001; 83.3% | |
| North America | 19 | 6.6% (5.1% - 8.4%) | 0.001; 56.5% | |
| Study design | ||||
| Observational | 114 | 7.2% (6.5% - 7.9%) | < 0.001; 65.4% | 0.897 |
| Clinical trial | 28 | 7.1% (5.7% - 8.7%) | < 0.001; 70.5% | |
| Treatment status | ||||
| Partial population treated | 8 | 5.9% (3.9% - 8.9%) | 0.168; 32.6% | 0.659 |
| Complete population treated | 76 | 7.2% (6.3% - 8.3%) | < 0.001; 72.1% | |
| Unknown/not treated | 58 | 7.1% (6.3% - 8.0%) | < 0.001; 57.3% | |
| Source | ||||
| Primary tumor | 34 | 7.5% (6.3% - 8.7%) | 0.152; 20.1% | 0.832 |
| Metastasis | 16 | 6.4% (3.8% - 10.6%) | < 0.001; 68.3% | |
| Both primary tumors and metastases | 20 | 7.1% (5.8% - 8.5%) | 0.039; 39.0% | |
| Mutation assessment methodb | ||||
| Gel electrophoresis methods | 6 | 4.5% (2.5% - 7.9%) | 0.754; 0.0% | |
| High-resolution melting | 13 | 8.0% (5.9% - 10.9%) | < 0.001; 79.0% | |
| Mass spectrometry | 13 | 5.4% (4.4% - 6.6%) | 0.044; 44.2% | |
| Multiplex mutation assays | 10 | 7.5% (5.8% - 9.6%) | 0.170; 29.9% | |
| Mutant allele specific PCR | 35 | 8.1% (7.0% - 9.2%) | < 0.001; 57.0% | |
| Next-generation sequencing | 6 | 7.4% (5.7% - 9.5%) | 0.974; 0.0% | |
| Not reported | 7 | 7.1% (4.6% - 10.9%) | 0.010; 64.2% | |
| Other | 6 | 3.9% (2.3% - 6.4%) | 0.004; 71.2% | |
| Pyrosequencing | 19 | 9.1% (7.2% - 11.4%) | < 0.001; 74.3% | |
| Sanger/direct sequencing (PCR) | 69 | 6.8% (6.1% - 7.6%) | 0.004; 33.6% | |
| Study quality score | ||||
| ≤ 16 | 70 | 7.2% (6.4% - 8.0%) | < 0.001; 58.5% | 0.803 |
| > 16 | 72 | 7.0% (6.1% - 8.1%) | < 0.001; 70.7% | |
| Study time period | ||||
| Pre-2007 | 10 | 6.3% (4.2% - 9.5%) | 0.038; 49.4% | 0.520 |
| Includes 2007 | 59 | 7.4% (6.2% - 8.7%) | < 0.001; 73.1% | |
| Post-2007 | 28 | 6.3% (4.2% - 9.5%) | 0.098; 26.7% | |
| Median length of follow-up time | ||||
| < 25 months | 12 | 9.7% (6.1% - 15.0%) | < 0.001; 71.9% | 0.271 |
| ≥ 25 months | 24 | 7.4% (6.1% - 8.8%) | 0.002; 51.6% | |
| Meta-regression on follow-up time | 36 | -0.005 (-0.015; 0.005) | N/A | 0.314 |
aGlobal exon estimate (most global estimate for a given exon contained within a manuscript); bCategories not mutually exclusive as some studies used multiple forms of mutation assessment methods, P value not calculated; cIndividual studies may contribute multiple prevalence estimates derived from independent study arms, so N refers to the number of independent prevalence estimates included in summary measure and may exceed the actual number of studies. mCRC: metastatic colorectal cancer; CI: confidence interval.