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Table 3 Comparison of patient survival according to the identified classifications with external validation and additional subgroups in the DACHS cohort

From: External validation of molecular subtype classifications of colorectal cancer based on microsatellite instability, CIMP, BRAF and KRAS

  Original studies DACHS study
Author / Population Subtypes MSI BRAF KRAS CIMP n (%) HR (95%CI) HR (95%CI) n (%) HRa (95%CI) HRa (95%CI)
Samadder et al. [20] 2013         CSS OS    CSS OS
Women, CRC Traditional 170 45.9 1 1 366 56.8 1 1
Serrated any + + 58 15.7 1.56 (0.9–2.8) 1.23 (0.8–1.8) 72 11.2 1.37 (0.7–2.5) 1.04 (0.6–1.7)
Alternate + 142 38.4 1.26 (0.7–2.4) 0.85 (0.6–1.3) 206 32 1.09 (0.7–1.6) 0.93 (0.7–1.3)
Total      370     644    
Men Traditional    Not reported in original study 598 65.5 1 1
Serrated any + +      32 3.5 0.89 (0.3–2.5) 0.95 (0.4–2.0)
Alternate +      283 31 1.21 (0.9–1.7) 1.24 (1.0–1.6)
Total          913    
Both sexes Traditional    Not reported in original study 964 61.9 1 1
Serrated any + +      104 6.7 1.35 (0.8–2.2) 1.09 (0.7–1.6)
Alternate +      489 31.4 1.15 (0.9–1.5) 1.08 (0.9–1.3)
Total          1557    
Phipps et al. [21] 2015         CSS OS    CSS OS
All stages, CRC Type 1 + + + 100 8.4 0.54 (0.3–1.0) 1.05 (0.8–1.4) 77 4.8 0.93 (0.5–1.8) 0.83 (0.5–1.4)
Type 2 + + 55 4.6 1.84 (1.2–2.8) 1.40 (1.0–2.0) 27 1.7 1.83 (1.0–3.4) 1.55 (0.9–2.7)
Type 3 + 353 29.7 1.25 (1.0–1.5) 1.23 (1.0–1.5) 489 30.4 1.18 (0.9–1.5) 1.13 (0.9–1.4)
Type 4 631 53.1 1 1 964 60 1 1
Type 5 + 50 4.2 0.42 (0.2–0.9) 0.74 (0.5–1.2) 50 3.1 1.04 (0.4–2.5) 1.51 (0.8–2.7)
Total      1189     1607    
Sinicrope et al. [16] 2015         DFS b     RFS  
Stage III, colon Non BRAF/KRAS   1331 48.9 1   137 49.1 1  
Chemotherapy Mut KRAS +   945 34.7 1.48 (1.3–1.7)   102 36.6 1.39 (0.8–2.4)  
N0147 trial Mut BRAF +   189 6.9 1.43 (1.1–1.8)   12 4.3 2.77 (1.1–7.2)  
dMMR sporadic + + any MLH1 184 6.8 1.10 (0.8–1.5)   16 5.7 1.15 (0.4–3.2)  
dMMR familial + any   71 2.6 0.77 (0.5–1.3)   12 4.3 0.33 (0.1–2.6)  
Total      2720     279    
All stages, colon Non BRAF/KRAS     Not reported in original study 578 51.3 1  
Mut KRAS +       361 32.1 1.31 (1.0–1.7)  
Mut BRAF +       53 4.7 3.01 (1.9–4.7)  
dMMR sporadic + + any MLH1      84 7.5 0.60 (0.3–1.1)  
dMMR familial + any       50 4.4 0.36 (0.1–1.0)  
Total          1126    
All stages, CRC Non BRAF/KRAS     Not reported in original study 1055 57.3 1  
Mut KRAS +       578 31.4 1.18 (1.0–1.4)  
Mut BRAF +       63 3.4 2.96 (2.0–4.4)  
dMMR sporadic + + any MLH1      84 4.6 0.54 (0.3–1.0)  
dMMR familial + any       60 3.3 0.58 (0.3–1.2)  
Total          1840    
  1. MSI microsatellite instability, dMMR deficient mismatch-repair, HR hazard ratio, CSS cancer-specific survival, OS overall survival, DFS disease-free survival, RFS relapse-free survival
  2. aAdjusted for what the original study adjusted for: Samadder et al.: Age, location, grade, stage, chemotherapy, radiotherapy. Phipps et al.: Age, sex, stage, BMI, year of diagnosis, smoking. Sinicrope et al.: Age, sex, location, T stage, N stage, grade, lymph nodes examined, chemotherapy
  3. bDFS: Defined as “time from date of randomization to first documented disease recurrence or death (due to all causes), whichever occurred first”. Approximated here with RFS