ABSTRACTS S45

instrumental variable, could provide clues to the best treatment strategy in

geriatric oncology.

Methods: Population-based national cohorts (2001-2010) from

Denmark (DK), Sweden (SE), Belgium (BE), the Netherlands (NL) and

Spain (ES), and a regional cohort from Italy (IT) were compared on treat-

ment strategy and Relative Survival, using country as instrumental vari-

able. Side-by-side comparisons were performed for DK-SE, BE-NL and

ES-IT. Differences between proportions of treatment were calculated,

stratified for stage. Relative Survival was calculated as the ratio of the sur-

vival observed and the expected survival based on the matched general

population in the specific countries.

Results: Overall, 16487 rectal cancer patients over the age of 80 years

were included in 6 countries. Relative Survival for stage III rectal cancer

was higher in SE (adjusted RER 0.7 (95%CI 0.6-0.9); p¼0.008 as

compared to DK), with a higher proportion receiving preoperative radio-

therapy (31.6% versus 9.7%). There were no survival differences between

BE and NL for stage I, II and III. For stage IV, there was a trend towards a

higher survival rate in BE (adjusted RER 1.1 (1.0-1.3); p¼0.06)) with a

higher proportion who had surgery and received chemotherapy in BE.

There were no survival differences between ES and IT.

Conclusion: The current comparison shows that the treatment strategy

in Sweden (with a higher proportion of preoperative radiotherapy) is asso-

ciated with a higher survival rate in stage III. Further detailed analyses of

patient selection criteria for specific treatments could lead to specific

RCTs, treatment strategy changes and tailored treatment for rectal cancer

patients over the age of 80 years.

No conflict of interest.

http://dx.doi.org/10.1016/j.ejso.2014.08.090

95. The relationship between the tumour microenvironment and

epithelial-mesenchymal transition in colorectal cancer

C.Y. Kong1, J.H. Park1, J. Edwards2, A. Powell1, L. Bennett2,

D.C. McMillan1, P.G. Horgan1, C.S. Roxburgh1

1 Glasgow Royal Infirmary University of Glasgow, Academic Unit of

Surgery, Glasgow, United Kingdom2 Institute of Cancer Sciences University of Glasgow, Unit of Experimental

Therapeutics, Glasgow, United Kingdom

Background: Epithelial-mesenchymal transition (EMT) is the process

whereby tumour epithelial cells dedifferentiate into mesenchymal cells,

therefore conferring these cells an invasive and metastatic phenotype.

EMT has been shown to be related to high-risk clinicopathologic factors

and poorer cancer specific survival in colorectal cancer. The relationships

between EMT and the tumour microenvironment however have not been

fully characterized.

Materials and Methods: The expression of E-cadherin, b-Catenin and

Zinc-finger-enhancing-binding-protein-1 (Zeb-1) was assessed by immu-

nohistochemistry in a tissue microarray comprising 272 patients with Stage

I-III colorectal cancer. Tissue specimens were taken from the tumour core.

The relationships between the expression of these biomarkers and clinico-

pathologic factors, tumour microenvironment factors and cancer specific

survival were assessed.

Results: Low membrane expression of E-cadherin was associated

with venous invasion (P ¼ 0.011). A high total Zeb-1 expression was asso-

ciated with peritoneal involvement and poor tumour differentiation (both

P ¼ 0.019). A low cytoplasmic b-Catenin expression was associated

with a weak Klintrup-Makinen score (P ¼ 0.027) and a high tumour

stroma percentage (P ¼ 0.020). An EMT score was computed which

comprised (1) low membrane E-cadherin, (2) absent membrane b-Catenin,

(3) increased nuclear b-Catenin and (4) high total Zeb-1. A high EMT

score was associated with a low Klintrup-Makinen score (P ¼ 0.050), a

low CD3 infiltrate and a low CD8 infiltrate at the invasive margin (P ¼0.01 and P ¼ 0.017, respectively). On multivariate analysis of tumour

microenvironment factors and TNM stage, a high EMT score was associ-

ated with poorer cancer specific survival (HR¼ 2.01 (95% CI ¼ 1.05-3.85)

P ¼ 0.034), independent of TNM stage (HR¼ 1.64 (95% CI ¼ 1.02-2.65)

P ¼ 0.042), CD3 infiltrate at the invasive margin (HR¼ 2.26 (95% CI ¼1.22-4.20) P ¼ 0.010) and tumour stromal percentage (HR¼ 2.14 (95%

CI ¼ 1.24-3.71) P ¼ 0.006). Further, a high EMT score was correlated

with poorer cancer specific survival in patients who were node-negative

and venous invasion negative (P ¼ 0.045).

Conclusions: This study shows that a combined EMT score as as-

sessed in the tumor core is associated with poorer cancer specific survival

in colorectal cancer independent of TNM stage and tumour microenviron-

ment and may also identify early stage patients at risk of recurrence. Addi-

tionally, it supports increasing evidence that EMT as assessed by its

biomarker alterations is not confined to the invasive margins of tumors.

Moreover, an increased immune reaction at the invasive margin was asso-

ciated with a low EMT score and may reflect the protective effect of adap-

tive in situ inflammatory responses in colorectal cancer.

No conflict of interest.

http://dx.doi.org/10.1016/j.ejso.2014.08.091

96. Differences in adjuvant chemotherapy administration for rectal

cancer patients - a EURECCA international comparison

A.J. Breugom1, P.G. Boelens1, L.H. Iversen2, L. P�ahlman3, H. Ortiz4,

R. Janciauskiene5, L. Van Eycken6, V. Valentini7, V.E. Lemmens8,

C.J.H. Van de Velde1

1 Leiden University Medical Center, Surgical Oncology, Leiden,

Netherlands2Danish Colorectal Cancer Group, Copenhagen, Denmark3Uppsala University, Surgical Sciences, Uppsala, Sweden4 Public University of Navarra, Surgery, Pamplona, Spain5 LIthuanian University of Health Sciences, Oncology, Kaunas, Lithuania6 Belgian Cancer Registry, Brussels, Belgium7Catholic University of Sacred Heart, Radiotherapy, Rome, Italy8 Comprehensive Cancer Center South, Eindhoven, Netherlands

Background: Considerable debate exists on the role of adjuvant

chemotherapy for rectal cancer patients after preoperative (chemo)radia-

tion and TME surgery, and trials did not give a definitive answer so far.

The aim of this large population-based international comparison, using

country as instrumental variable, is to compare treatment strategies and

survival in rectal cancer patients among seven European countries. This

could lead to new insights on the value of adjuvant chemotherapy for rectal

cancer patients

Material and methods: We used population-based national cohorts

from Belgium (BE), the Netherlands (NL), Sweden (SE), Denmark

(DK), and Spain (ES), as well as two regional cohorts from Italy (IT),

and Lithuania (LT), including operated stage I-III rectal cancer patients

diagnosed between 2004 and 2009. Country will be used as instrumental

variable.

The proportion of adjuvant chemotherapy administration was

compared, stratified by stage. Relative survival will be calculated for all

participating countries defined as the ratio of observed survival to the ex-

pected survival based on the matched general population.

Results: We included a total of 35.830 operated rectal cancer patients

aged 18 years and older in seven countries. The proportion of adjuvant

chemotherapy administration varied between 1.2% (SE) and 52.1% (ES)

for stage I rectal cancer (including patients who were downstaged after

chemoradiation), between 3.0% (NL) and 65.5% (ES) for stage II rectal

cancer, and between 12.1% (LT) and 69.1% (ES) for stage III rectal cancer.

Relative survival will be calculated, and will also be presented during the

congress.

Conclusion: This international comparison demonstrates large varia-

tion in the use of adjuvant chemotherapy between seven European coun-

tries. The final results of this study could lead to changes in adjuvant

treatment administration, and has the ultimate goal to provide a better

founded and individualised guideline for stage I-III rectal cancer patients.