Impact of the Type and Modalities of Preoperative Chemotherapy on the Outcome of Liver Resection for Colorectal Metastases R. Adam, E. Barroso, C. Laurent,

Impact of the Type and Modalities of Preoperative Chemotherapy on the Outcome of Liver Resection for

Colorectal Metastases

R. Adam, E. Barroso, C. Laurent, G. Nuzzo, C. Hubert, G. Mentha, J. Ijzermans, L. Capussotti, S. Lopezben, D. Mirza, G. Kaiser, E. Oussoultzoglou, T. Gruenberger, G. J. Poston, O. Skipenko, and The LiverMetSurvey Centers

Impact of the type and modalities of preoperative chemotherapy on the

outcome of liver resection for colorectal metastases

R. Adam, E. Barroso, C. Laurent, G. Nuzzo, C. Hubert, G. Mentha, J. Ijzermans, L. Capussotti, S. Lopez-Ben, D. Mirza, G. Kaiser, E. Housseau, T. Gruenberger,

G. J. Poston, O. Skipenko, The LiverMetSurvey Centers

LiverMetsurveyBackground

Prognostic factors of survival have been extensively reported after resection of colorectal liver metastases.

However, a specific analysis of patients submitted to preoperative chemotherapy (PCT), with the real impact of type and modalities of treatment on patient outcome is lacking.

LiverMetsurveyAim of the study

To evaluate impact of the type and modalities of PCT on the long-term outcome of resected patients for colorectal liver metastases in a large multicenter cohort, LiverMetsurvey.

LiverMetsurveyNumber of patients

LiverMetsurveyStudy design

LiverMetsurvey

Jan 1995 – June 2010

8912 Patients – 151 Centers in 39 Countries

No Preop Chemotherapy4468

Preop Chemotherapy4444

49.9%

Study population

LiverMetsurveyPatients and Methods

LiverMetSurvey is an international, internet-based prospective registry designed to assess the efficacy of multimodality treatment options for colorectal liver metastases (CLM) . 4444 patients (49.9%) received chemotherapy before liver resection. The distribution of potential prognostic factors including age, sex, primary tumor site, timing of metastasis diagnosis, tumor number, diameter of the largest metastasis, bilaterality, initial resectability, and type and duration of chemotherapy were compared to overall (OS) and disease-free (DFS) survivals using univariate and multivariate analyses.

LiverMetsurveyOverall Survival : Global Population

Without Preop. chemo

With Preop. chemo

No of exposed pts

Preop. chemo

65%

58% 47%

39%

LiverMetsurveyOverall Survival : Initially resectable patients

No of exposed pts

Preop. chemo

Without Preop. chemo

With Preop. chemo

65%

62%47%

44%

LiverMetsurveyOverall Survival : Initially non resectable patients

No of exposed pts

Preop. chemo

Without Preop. chemo

With Preop. chemo

54%

50%33%

33%

LiverMetsurveyPatients and Tumour Characteristics (1)

Characteristics

MaleAge (yrs,mean±sd)Tumor localization

Left including sigmoidRectumRightTransverseMultiple localizations

Metast. primary lymph nodesNo meta. at diagnosis

1-34-7>7

Meta. at diagnosis ≥ 30mm

No chemo preop

62.3%64 ± 11

42.3%32.1%18.7%3.5%3.4%

60.7%

88.9%8.9%2.2%

56.6%

Chemo preop

62.1%61 ± 11

46.3%30.7%16.9%3.2%3.0%

66.6%

67.5%23.8%8.7%

59.5%

P

NS< 0.0001

0.005

< 0.0001

< 0.0001

0.01

LiverMetsurveyPatients and Tumour Characteristics (2)

Characteristics

Synchronous

Initial resectability

Bilateral localization

Abnormal prehep CEA level (>5)

Concomitant extrahepatic disease

Major hepatectomy

R2 resection

Combined techniques

Post-op chemotherapy

Center volume (mean±sd)(Max done in a year)

No chemo preop

38.4%

95.0%

23.8%

67.0%

8.6%

46.2%

6.7%

14.1%

47.4%

45.1 ± 33.1

Chemo preop

68.7%

62.8%

49.0%

58.1%

12.8%

63.6%

12.9%

28.2%

57.9%

57.8 ± 38.4

P

< 0.0001

< 0.0001

< 0.0001

< 0.0001

< 0.0001

< 0.0001

< 0.0001

< 0.0001

< 0.0001

< 0.0001

LiverMetsurveyPatients with preoperative chemotherapy

No of exposed pts

Overall Survival Disease Free Survival(Non palliative pts)

90%

62%58%

30%

LiverMetsurvey - Overall survivalPatients with preoperative chemotherapy

Multivariate Analysis

Risk factors

Metastatic primary lymph nodes

Abnormal CEA levels (>5)

Concomitant extrahepatic disease

Metastases >3

Tumoral progression

Type of chemotherapy

More than 1 line of Chemo.

R2 resection

P

0.005

< 0.0001

< 0.0001

0.006

0.04

NS

0.0002

< 0.0001

RR

1.29

1.46

1.66

1.29

1.31

-

1.45

1.65

CI 95%

[1.1-1.5]

[1.2-1.7]

[1.4-2.0]

[1.1-1.5]

[1.0-1.7]

-

[1.2-1.8]

[1.3-2.1]

LiverMetsurvey - Overall survivalPatients with preoperative chemotherapy

No of exposed ptsMetastatic primary lymph nodes

No metastatic primary lymph nodes

Metastatic primary lymph nodes

67%

54%47%

35%

LiverMetsurvey - Overall survivalPatients with preoperative chemotherapy

No of exposed ptsConcomitant extrahep. metastases

No concomitant extrahep. metastases

Concomitant extrahep. metastases

60%

42% 42%

18%

No of exposed pts

Prehep. CEA ≥ 5

Prehep. CEA < 5 ng/ml

Prehep. CEA ≥ 5 ng/ml

LiverMetsurvey - Overall survivalPatients with preoperative chemotherapy

67%

52%49%

31%

No of exposed pts

Pre-op last line result

No preop. Progression

Preop. Progression

LiverMetsurvey - Overall survivalPatients with preoperative chemotherapy

59%

42%

41%

23%

No of exposed pts

No Metastases at diagnosis

> 3 Metastases

1-3 Metastases

LiverMetsurvey - Overall survivalPatients with preoperative chemotherapy

63%

51%46%

31%

No of exposed pts

Liver curative

Palliative resection

Curative resection

LiverMetsurvey - Overall survivalPatients with preoperative chemotherapy

62%

36%

43%

20%

No of exposed pts

No lines preop

> 1 line chemotherapy

Only 1 line chemotherapy

LiverMetsurvey - Overall survivalPatients with preoperative chemotherapy

59%

51% 42%

27%

LiverMetsurvey - Overall survivalPatients with preoperative chemotherapy

No of exposed ptsPreop. Chemo. type

Irino-based

Oxali-based

Oxali-Irino-based

61%

57%41%

34%

No of exposed pts

Preop. Targeted therapy

No preop. Targeted therapy

Preop. Targeted therapy

LiverMetsurvey - Overall survivalPatients with Oxaliplatin-based preop. chemo.

62%

58% 48%

41%

No of exposed pts

Preop. Targeted therapy

No preop. Targeted therapy

Preop. Targeted therapy

LiverMetsurvey - Overall survivalPatients with Irinotecan-based preop. chemo.

58%

56%54%

40%

No of exposed pts

Preop. Targeted therapy

No preop. Targeted therapy

Preop. Targeted therapy

LiverMetsurvey - Overall survivalPatients with Oxali-Irino-based preop. chemo.

70%

56%42%

34%

No of exposed pts

Preop. Targeted therapy

LiverMetsurvey - Overall survivalPatients with preoperative chemotherapy

No preop. Targeted therapy

Preop. Targeted therapy

59%

58% 48%

39%

No of exposed ptsPreop. Targeted therapy

Bevacizumab

Cetuximab/Panitumumab

Without Preop. Targeted therapy

LiverMetsurvey - Overall survivalPatients with preoperative chemotherapy

59%

57% 50%

39%

Risk factors

Metastatic primary lymph nodes

Abnormal CEA levels (>5)

Metastases >3

Tumoral progression

Type of chemotherapy

Major hepatectomy

More than 6 cycles

P

0.0008

0.005

0.0001

0.05

NS

0.04

0.004

RR

1.32

1.25

1.4

1.3

-

1.2

1.25

CI 95%

[1.1-1.6]

[1.1-1.5]

[1.2-1.7]

[1.0-1.7]

-

[1.0-1.4]

[1.1-1.5]

LiverMetsurvey – Disease free survivalPatients with preoperative chemotherapy

Multivariate Analysis

LiverMetsurvey – Disease free survivalPatients with preoperative chemotherapy

No of exposed pts

No cycles preop

> 6 cycles

1-6 cycles

33%

25%

26%

17%

LiverMetsurveyConclusion

Preoperative Chemotherapy is used in half patients overall, 63% of whom with initially resectable CLM.

The type of Chemotherapy does not influence the outcome provided that resection is achieved.

However, the shorter is the Chemotherapy and the more limited is the number of lines, the best is the survival after surgery.

LiverMetsurvey - Overall survivalPatients with preoperative chemotherapy

No of exposed ptsInitially resectable

Not initially resectable

Initially resectable

62%

54% 44%

33%