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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
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