SUPPLEMENTARY MATERIAL Local Treatment of Unresectable Colorectal Liver Metastases: Results of a Randomized Phase II Trial

SUPPLEMENTARY MATERIAL

Local Treatment of Unresectable Colorectal Liver Metastases: Results of a Randomized Phase II Trial

Theo Ruers¹, Frits Van Coevorden¹, Cornelis Punt², Jean-Pierre E.N Pierie³, Inne Borel-Rinkes⁴, Jonathan A. Ledermann⁵, Graeme Poston⁶, Wolf Bechstein⁷,

Marie-Ange Lentz⁸, Murielle Mauer⁹, Gunnar Folprecht¹⁰, Eric Van Cutsem¹¹, Michel Ducreux¹², Bernard Nordlinger¹³

For the EORTC Gastro-Intestinal Tract Cancer Group, Arbeitsgruppe Lebermetastasen und –tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie (ALM-CAO) and the National Cancer Research Institute Colorectal Clinical Study Group (NCRI CCSG)

1The Netherlands Cancer Institute - Antoni Van Leeuwenhoek Ziekenhuis, Amsterdam, The Netherlands

2Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands

3Leeuwarden Medical Center, Leeuwarden, The Netherlands

4Universitair Medisch Centrum, Academisch Ziekenhuis, Utrecht, The Netherlands

5Cancer Research UK and UCL Cancer Trials Centre and UCL Hospitals, London, United Kingdom

6Aintree University Hospital, Liverpool, United Kingdom

7Frankfurt University Hospital and Clinics, Frankfurt, Germany

8EORTC Headquarters, Data Management Unit, Brussels, Belgium

9EORTC Headquarters, Statistics Department, Brussels

10University Cancer Center, University Hospital Carl Gustav Carus, Dresden, Germany

11Digestive Oncology, University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium

12 Institut Gustave Roussy, Villejuif, France – ¹³ Ambroise Paré, Assistance Publique Hôpitaux de Paris, Boulogne- Billancourt, France

Corresponding Author Prof dr T. Ruers

Head of the Division Surgical Oncology The Netherlands Cancer Institute, Amsterdam

Tel: +31 20 5122538 Fax: +31 20 5122554 E-mail: T.Ruers@nki.nl

Supplementary Table 1. Survival after initial disease progression

Survival after initial progression Non-parametric Cox model

Treatment No. of

Patients Observed

Events Median (95% CI),

months % Survival at 5

years (95% CI) P-Value* Hazard Ratio (95% CI)

Systemic 55 51 20.99 (16.16-30.52) 11.1 (4.5-21.1) 0.48 1.00

Local+Systemic 43 37 19.48 (14.32-32.26) 16.3 (7.2-28.7) 0.86 (0.56-1.31)

* P value was calculated using a two-sided log-rank test. CI=confidence interval

Supplementary Figures

Supplementary Figure 1. Sensitivity analysis of Overall Survival, adjusted for number of liver metastases

). P value for treatment effect was calculated using a stratified log- rank test. Heterogeneity was tested using a Cochran’s Q test. All statistical tests were two- sided. HR=hazard ratio. CI=confidence interval. Q=Cochran's heterogeneity statistic.

df=degrees of freedom. I

= I² statistic.

Supplementary Figure 2. Sensitivity analysis of Overall Survival, adjusted for

synchronicity (synchronous vs. metachronous). P value for treatment effect was calculated

using a stratified log-rank test. Heterogeneity was tested using a Cochran’s Q test. All statistical

tests were two-sided. HR=hazard ratio. CI=confidence interval. Q=Cochran's heterogeneity

statistic. df=degrees of freedom. I

= I² statistic.

(years)

0 2 4 6 8 10

0 10 20 30 40 50 60 70 80 90 100

O N Number of patients at risk : Treatment

51 55 25 11 5 1

37 43 19 10 7 5

Systemic Local+Systemic

Survival probability (%)

Overall Logrank test: p=0.48

Supplementary Figure 3. OS after initial disease progression. P value was calculated using

a two-sided log-rank test. O=number of events. N=number of patients.