Table 1.
Studies on prognostic significance of PIK3CA exon 9 and 20 mutations in colorectal cancer
| Ref. | Authors (year) | No. of hospitals | Total no. of events* | Sample size | Tumor location | Disease stage | No. of PIK3CA mutants
|
BRAF data | KRAS data | CS, OS, DFS, RFS or PFS log-rank P value | Multivariate HR (95% CI), P value | Notes and/or a list of variables examined in multivariate analysis | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Exon 9 | Exon 20 | ||||||||||||
| 4 | Kato et al. (2007) | 1 | 32 | 158 | Colon & rectum | II/III | 11 | 7 | No | Yes |
P = 0.022 (RFS) P = 0.036 (CS) |
2.48 (1.03 – 5.97) P = 0.043 (RFS) Exon 9 or 20 |
Lymph node metastasis, CEA level, tumor size and lymphatic invasion. |
| 6 | Abubaker et al. (2008) | 1 | N/A | 418 | Colon & rectum | I–IV | 38 | 13 | No | No | NS (OS) | Exon 9 or 20 | |
| 9 | Barault et al. (2008) | 3 | 197 | 586 | Colon | I–IV | 46 | 29 | Yes | Yes | N/A | N/A Exon 1, 2, 9 or 20 |
PIK3CA, KRAS and BRAF mutations were not evaluated separately. |
| 10 | Souglakos et al. (2009) | 2 | 43 | 92 | Colon & rectum | I–IV | 18 | 8 | Yes | Yes | NS (OS) | 2.1 (1.2 – 3.9) P = 0.01 (PFS) Exon 9 or 20 |
Age, tumor grade, metastatectomy, tumor location and number of treatment lines (1 vs >3). Patients with metastatic colorectal cancer after cetuximab treatment. |
| 13 | Sartore- Bianchi et al. (2009) | 2 | 88 | 110 | Colon & rectum | III–IV | 4 | 11 | No | Yes | P =0.0035 (PFS) | Exon 9 or 20 | |
| 14 | Ogino et al. (2009) | Many | 152 | 450 | Colon | I–III | 82 | Yes | Yes | P = 0.075 (CS) | 2.23 (1.21–4.11) (CS) Exon 9 or 20 |
Age, sex, body mass index, year of diagnosis, tumor location, stage, grade and status of MSI, CIMP, KRAS, BRAF, LINE-1 methylation and TP53. | |
| 15 | He et al. (2009) | Many | 84 | 240 | Rectum | I–III | 12 | 7 | Yes | Yes |
P = 0.008 (LR) NS (OS) |
3.4 (1.2–9.2) P = 0.017 (LR) Exon 9 or 20 |
TNM stage, circumferential margin. |
| 16 | De Roock et al. (2010) | 11 | N/A | 743 | Colon & rectum | IV | 74 | 22 | Yes | Yes |
P = 0.013 (PFS) P =0.0057 (OS) |
2.27 (1.10 – 4.66) P = 0.042 (PFS) 3.30 (1.46 – 7.45) P = 0.012 (OS) Exon 20 |
Age, sex, number of previous chemotherapy lines, center, mutation status of KRAS, BRAF and NRAS. Exon 9 mutation was not associated with outcome. |
| 17 | Tol et al. (2010) | Many | N/A | 436 | Colon & rectum | IV | 32 | 11 | Yes | Yes | NS (PFS, OS) | Exon 9 or 20 | Serum LDH, number of affected organs and previous adjuvant therapy. |
| 18 | Farina Sarasqueta et al. (2011) | ? | ? | 685 | Colon | I–III | 66 | 17 | No | No |
P = 0.04 (DFS) P = 0.03 (CS) |
Exon 20 | Exon 9 mutation was not associated with outcome. |
| Liao et al. (current study) | Many | 552 | 1170 | Colon & rectum | I–IV | 116 | 80 | Yes | Yes |
P = 0.031 (CS) P =0.0008 (OS) |
3.51 (1.28–9.62) (CS) 2.68 (1.24 – 5.77) (OS) Cases with mutations in both exons 9 and 20 1.05 (0.71–1.56) (CS) 0.90 (0.67–1.22) (OS) Cases with exon 9 mutation alone 0.96 (0.59–1.55) (CS) 0.80 (0.55–1.16) (OS) Cases with exon 20 mutation alone 1.07 (0.79–1.45) (CS) 0.91 (0.72–1.15) (OS) Cases with mutations in either or both of exons 9 and 20 |
Age, sex, year of diagnosis, tumor location, stage, grade and status of MSI, CIMP, KRAS, BRAF and LINE- 1 methylation. | |
CI, confidence interval; CIMP, CpG island methylator phenotype; CS, cancer specific survival; DFS; disease free survival; HR, hazard ratio; LR, local recurrence; MSI, microsatellite instability; N/A, not available; NS, not significant; OS, overall survival; PFS, progression free survival, RFS, relapse free survival.
*
, relapses or deaths.