Table 4 Association of baseline characteristics, treatment, and response parameters with relapse-free and overall survival

From: Differential histopathologic parameters in colorectal cancer liver metastases resected after triplets plus bevacizumab or cetuximab: a pooled analysis of five prospective trials

   

Univariate analysis

Multivariate analysis

p

 

N

Median

HR for RFS (95% CI)

p

HR for RFS (95% CI)

 

Baseline characteristics

 >ECOG PS

  0

152

12.2

1

 

—

 

  1–2

7

13.4

1.03 (0.39–2.76)

0.953

—

—

 Time to metastases

  Synchronous

131

11.0

1

 

1

 

  Metachronous

28

19.8

0.59 (0.41–0.96)

0.034

0.95 (0.53–1.70)

0.854

 No. of liver metastases

  ≥4

59

9.3

1

 

1

 

  <4

93

19.8

0.62 (0.40–0.91)

0.018

0.92 (0.49–1.72)

0.804

  NA

7

—

—

   

 Primary resected

  No

39

9.7

1

 

1

 

  Yes

120

13.8

0.61 (0.34–0.91)

0.020

0.50 (0.17–1.50)

0.221

 Location of primary tumour

  Right colon

40

11.3

1

 

—

 

  Left colon

116

12.0

0.81 (0.52–1.23)

0.301

—

—

  NA

3

—

—

 

—

 

 Nodal status of primary tumour

  Node positive

85

12.6

1

 

1

 

  Node negative

35

37.1

0.53 (0.36–0.85)

0.009

0.50 (0.28–0.88)

0.018

  NA

39

—

—

 

—

 

 Tumour size, diameter

  >5 cm

56

11.0

1

 

—

 

  ≤5 cm

102

12.7

1.00 (0.68–1.48)

0.993

—

—

  NA

1

—

—

 

—

 

 Distribution of liver metastases

  Bilobar

96

10.4

1

 

1

 

  Unilobar

54

16.7

0.68 (0.47–1.01)

0.058

0.95 (0.52–1.72)

0.864

  NA

9

—

—

   

 No. of involved segments

  >6

19

9.2

1

 

—

 

  ≤6

116

13.8

0.71 (0.32–1.37)

0.273

—

—

  NA

24

—

—

 

—

 

 Disease-free interval

  <12 months

137

11.3

1

 

—

 

  >12 months

22

13.3

0.88 (0.54–1.46)

0.220

—

—

 Mutational status

  RAS/BRAF wt

91

12.6

1

 

—

 

  RAS mut

57

12.7

0.93 (0.63–1.38)

0.729

—

—

  BRAF mut

6

2.4

1.99 (0.66–10.57)

0.170

—

—

  NA

5

—

—

   

 CEA

  <200 ng/ml

112

11.0

1

 

—

 

  >200 ng/ml

21

13.8

0.91 (0.50–1.63)

0.740

—

—

  NA

26

—

—

   

 Treatment

  Targeted agent

  Cetuximab

56

10.4

1

 

—

 

  Bevacizumab

103

12.7

0.87 (0.59–1.27)

0.463

—

—

 Targeted agent (wt only)

  Cetuximab

56

10.4

1

 

—

 

  Bevacizumab

35

21.5

0.67 (0.41–1.14)

0.151

—

—

 Chemotherapy backbone

  FOLFOXIRI

92

16.7

1

 

1

 

  COI

67

17.7

0.64 (0.45–0.94)

0.022

0.74 (0.44–1.26)

0.277

Response parameters

 RECIST response

  >No

24

5.9

1

 

1

 

  Yes

134

13.4

0.53 (0.29–0.97)

0.040

0.67 (0.36–1.28)

0.231

  NA

1

—

—

   

 Early response

  No

23

4.9

1

 

—

 

  Yes

125

13.0

0.52 (0.23–0.72)

0.005

—

—

  NA

11

—

—

   

 Deepness of response

  Per 10% increase

121

—

0.96 (0.87–1.05)

0.350

—

—

 Tumour regression grade

  Partial/no histopathologic response (TRG3–4–5)

118

11.0

1

 

1

 

  Major histopathologic response (TRG1–2)

41

21.0

0.56 (0.40–0.89)

0.012

0.41 (0.21–0.79)

0.008

  NA

1

—

    

 Resection margins

  R0

133

12.7

1

 

—

 

  R1

26

10.4

1.02 (0.63–1.67)

0.931

—

—

Baseline characteristics

 ECOG PS

  0

152

46.0

1

 

1

 

  1–2

7

23.3

2.86 (1.19–31.75)

0.032

6.25 (0.67–58.09)

0.109

 Time to metastases

  Synchronous

131

41.6

1

 

1

 

  Metachronous

28

Undef

0.53 (0.33–1.04)

0.068

0.97 (0.27–3.43)

0.958

 No. of liver metastases

  ≥4

59

34.8

1

 

1

 

  <4

93

51.0

0.50 (0.29–0.83)

0.008

1.20 (0.32–4.41)

0.789

  NA

7

—

—

 

—

 

 Primary resected

  No

39

33.4

1

 

1

 

  Yes

120

44.6

0.59 (0.28–0.99)

0.051

0.84 (0.09–7.84)

0.879

Location of primary tumour

  Right colon

40

42.7

1

 

—

 

  Left colon

116

43.2

0.96 (0.55–1.70)

0.896

—

 

  NA

3

—

—

 

—

 

 Nodal status of primary tumour

  Node positive

85

42.4

1

 

1

 

  Node negative

35

58.6

0.54 (0.31–1.07)

0.080

0.45 (0.14–1.42)

0.175

  NA

39

—

—

 

—

 

 Tumour size, diameter

  >5 cm

56

36.5

1

 

—

 

  ≤5 cm

102

58.6

0.69 (0.40–1.14)

0.143

—

 

  NA

1

—

—

 

—

 

 Distribution of liver metastases

  Bilobar

96

36.5

1

 

1

 

  Unilobar

54

58.6

0.52 (0.32–0.91)

0.021

0.69 (0.24–1.98)

0.496

  NA

9

—

—

   

 No. of involved segments

  >6

19

33.4

1

 

1

 

  ≤6

116

46.6

0.43 (0.11–0.79)

0.016

2.06 (0.36–11.89)

0.422

  NA

24

—

—

 

—

 

 Disease-free interval

  <12 months

137

42.4

1

 

—

 

  >12 months

22

43.2

0.82 (0.43–1.61)

0.589

—

—

 Mutational status

  RAS/BRAF wt

91

46.0

1

 

1

 

  RAS mut

57

42.7

1.16 (0.67–2.03)

0.580

1.77 (0.80–3.94)

0.873

  BRAF mut

6

18.7

6.71 (2.36–180.20)

<0.001

3.80 (0.30–210.50)

0.632

  NA

5

—

—

   

 CEA

  <200 ng/ml

112

34.9

1

 

1

 

  >200 ng/ml

21

58.6

0.57 (0.22–1.10)

0.089

0.48 (0.15–1.54)

0.220

  NA

26

—

—

 

—

 

Treatment

 Targeted agent

  Cetuximab

56

46.6

1

 

—

 

  Bevacizumab

103

42.4

1.21 (0.75–2.00)

0.445

—

—

 Targeted agent (wt only)

  Cetuximab

56

46.6

1

 

—

 

  Bevacizumab

35

34.8

1.08 (0.50–2.35)

0.839

—

—

 Chemotherapy backbone

  FOLFOXIRI

92

36.5

1

 

1

 

  COI

67

64.3

0.52 (0.33–0.90)

0.019

0.94 (0.27–3.31)

0.928

 RECIST response

  No

24

29.5

1

 

1

 

  Yes

134

46.0

0.58 (0.23–1.13)

0.098

0.51 (0.17–1.55)

0.239

  NA

1

—

—

   

 Early response

  No

23

21.3

1

 

—

 

  Yes

125

46.0

0.45 (0.16–0.74)

0.006

—

—

  NA

11

—

—

   

 Deepness of response

  Per 10% increase

121

—

0.95 (0.84–1.06)

0.343

—

—

 Histopathologic response

  Partial/no response (TRG3–4–5)

118

42.1

1

 

1

 

  Major response (TRG1–2)

41

Undef

0.51 (0.32–0.99)

0.045

0.26 (0.07–0.89)

0.033

  NA

1

—

    

 Resection margins

  R0

133

42.7

1

   

  R1

26

70.1

0.67 (0.37–1.34)

0.284

  
  1. The "p" in bold indicate the p value statistically significant
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