- Email: [email protected]
96. Differences in adjuvant chemotherapy administration for rectal cancer patients - a EURECCA international comparison
ABSTRACTS 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 treatment strategy and Relative Survival, using country as instrumental variable. 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 survival 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 radiotherapy (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 associated 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 Kingdom 2 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 immunohistochemistry 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 clinicopathologic 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 associated 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 ¼ 0.01 and P ¼ 0.017, respectively). On multivariate analysis of tumour microenvironment factors and TNM stage, a high EMT score was associated with poorer cancer specific survival (HR¼ 2.01 (95% CI ¼ 1.05-3.85)
S45 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 ¼ 1.22-4.20) 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 assessed in the tumor core is associated with poorer cancer specific survival in colorectal cancer independent of TNM stage and tumour microenvironment and may also identify early stage patients at risk of recurrence. Additionally, 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 associated with a low EMT score and may reflect the protective effect of adaptive 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, Netherlands 2 Danish Colorectal Cancer Group, Copenhagen, Denmark 3 Uppsala University, Surgical Sciences, Uppsala, Sweden 4 Public University of Navarra, Surgery, Pamplona, Spain 5 LIthuanian University of Health Sciences, Oncology, Kaunas, Lithuania 6 Belgian Cancer Registry, Brussels, Belgium 7 Catholic University of Sacred Heart, Radiotherapy, Rome, Italy 8 Comprehensive Cancer Center South, Eindhoven, Netherlands Background: Considerable debate exists on the role of adjuvant chemotherapy for rectal cancer patients after preoperative (chemo)radiation 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 expected 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 variation in the use of adjuvant chemotherapy between seven European countries. 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.
S46 No conflict of interest. http://dx.doi.org/10.1016/j.ejso.2014.08.092
97. Intraoperative red blood cell salvage in locally recurrent rectal cancer patients S. Bosman1, F.A. Holman2, G.A.P. Nieuwenhuijzen1, H.J.T. Rutten1 1 Catharina Hospital, Surgery, Eindhoven, Netherlands 2 Leids University Medical Centre, Surgery, Leiden, Netherlands
ABSTRACTS 98. The effect of minimal invasive surgery on postoperative mortality in colorectal cancer surgery L. Gietelink1, M.W.J.M. Wouters2, R.A.E.M. Tollenaar1, P.J. Tanis3 1 Leiden University Medical Center, Surgery, Leiden, Netherlands 2 Netherlands Cancer Institute-Antoni van Leeuwenhoek, Surgery, Amsterdam, Netherlands 3 Academic Medical Center, Surgery, Amsterdam, Netherlands
Background: Surgical resection of local recurrent rectal cancer (LRRC) is often challenging. The anatomy is disturbed after prior surgery for the primary tumour. To achieve a radical resection, an extra anatomical resections is often required. These comprehensive procedures are often associated with increased blood loss and relatively high morbidity and mortality rates. It is unclear if it is safe to use intraoperative red blood cell salvage (ICS) in the treatment of patients with local recurrent rectal cancer. The objective of this study is to evaluate if the use of autologous blood through the cell saver is safe in patients with LRRC, regarding survival and complication rates. Material and methods: The Catharina hospital is a national referral centre for patients with recurrent rectal cancer. The Amount of blood products, the quantity of blood aspirated by the ICS and the blood volume returned to the patients was registered. Patient follow up was enrolled in a database; complications post-operative, presence of local recurrence, metastasis and overall survival was reported. Follow up ranged from 0 to 227 months, with a median of 40 months. Results: From 1994 until 2013, a total of 264 patients (mean age 63 year; 159 male, 105female) were treated with curative surgery. Patients were subdivided in two groups: patients who did or did not receive blood from the ICS. The mean blood loss was 6705cc (range 0-34000cc) of which 1533cc (range 72-6300cc) was returned with the ICS during surgery. The amount of blood loss was larger in the ICS group in contrast to patients in the non ICS group with an amount of blood loss >5L 65% vs 27%. More intra-abdominal abscesses occurred in the ICS group compared to the non ICS group (13% vs 2%), most likely due to the higher amount of blood loss in the ICS group. Multivariable analysis showed no influence of blood loss or blood products influencing the oncological outcome. The 5 year cancer specific, distant metastasis free, local recurrence free, relapse free and overall survival was 41, 49, 52, 33 and 35% respectively. The survival rates between the two groups did not differ significantly. Conclusions: The use of the cell saver in the treatment of patients with LRRC is safe and does not lead to additional complications. No disadvantageous effects were found concerning the oncological outcome, when comparing patients treated with the ICS and patients treated without the ICS. The use of the ICS should not be omitted because of fear for worse oncological outcome and should be implemented in the treatment of patients with LRRC. No conflict of interest.
Background: The use of minimal invasive surgery in colorectal cancer care has several potential benefits due to the causation of less surgical trauma. It potentially leads to a reduction of postoperative mortality, especially in high-risk patients. Meta-analyses, comparing laparoscopic to conventional surgery, showed a trend towards lower postoperative mortality, but were not able to show significant differences due to small sample sizes and relatively young and healthy study populations. Population studies, with a higher number of patients and events, did show significant reduction in casemix corrected postoperative mortality for minimal invasive surgery. The question remains whether selection bias (based on non measured casemix factors) were the cause of these results. As an alternative for casemix adjusted analyses, comparisons were made between elective open and laparoscopic resections in subgroups with similar operative risks as to minimalize this selection bias. Materials and methods: Data from the Dutch Surgical Colorectal Audit of 2010 to 2013 was used. All patients who underwent a resection for a primary colorectal tumor were analyzed. Subgroups with similar operative risks, based on age, ASA classification, tumor stage and previous abdominal surgery were formed and crude mortality rates were compared between laparoscopic and conventional surgery in each group. The influence of the laparoscopic approach on specific postoperative complications was analyzed in a univariate and multivariate model. Secondly, hospitals were divided into three tertiles according to their percentage of laparoscopic resections. Casemix corrected outcome measurements were calculated for all patients (laparoscopic/open surgery together) and compared between these tertiles. Results: For these analyses 35450 patients were included. Crude mortality rates were lower after laparoscopic resection in most subgroups. The highest absolute benefit was found for high-risk patients. Mortality rates after open and laparoscopic resection were 9.9 versus 6.7 percent respectively (p¼0.003) for patients with high operative risk. Furthermore, the laparoscopic approach was independently associated with a lower risk of cardiac (OR 0,66; 95%CI 0,58-0,74) and respiratory (OR 0,64; 95%CI 0,58-0,71) complications. Hospitals with a high percentage of laparoscopic resections showed an overall better performance on several casemix adjusted outcome parameters. Conclusions: These analyses convincingly show the positive influence of minimal invasive surgery on several postoperative outcomes. In most groups of patients the postoperative mortality was lower after a minimal invasive approach with the greatest advantage in groups with greater operative risk. Therefore it seems reasonable that, when both surgical techniques are possible, minimal invasive surgery has the preference over conventional surgery. No conflict of interest.
http://dx.doi.org/10.1016/j.ejso.2014.08.093
http://dx.doi.org/10.1016/j.ejso.2014.08.094
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 Kingdom 2 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 immunohistochemistry 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 clinicopathologic 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 associated 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 ¼ 0.01 and P ¼ 0.017, respectively). On multivariate analysis of tumour microenvironment factors and TNM stage, a high EMT score was associated with poorer cancer specific survival (HR¼ 2.01 (95% CI ¼ 1.05-3.85)
S45 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 ¼ 1.22-4.20) 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 assessed in the tumor core is associated with poorer cancer specific survival in colorectal cancer independent of TNM stage and tumour microenvironment and may also identify early stage patients at risk of recurrence. Additionally, 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 associated with a low EMT score and may reflect the protective effect of adaptive 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, Netherlands 2 Danish Colorectal Cancer Group, Copenhagen, Denmark 3 Uppsala University, Surgical Sciences, Uppsala, Sweden 4 Public University of Navarra, Surgery, Pamplona, Spain 5 LIthuanian University of Health Sciences, Oncology, Kaunas, Lithuania 6 Belgian Cancer Registry, Brussels, Belgium 7 Catholic University of Sacred Heart, Radiotherapy, Rome, Italy 8 Comprehensive Cancer Center South, Eindhoven, Netherlands Background: Considerable debate exists on the role of adjuvant chemotherapy for rectal cancer patients after preoperative (chemo)radiation 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 expected 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 variation in the use of adjuvant chemotherapy between seven European countries. 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.
S46 No conflict of interest. http://dx.doi.org/10.1016/j.ejso.2014.08.092
97. Intraoperative red blood cell salvage in locally recurrent rectal cancer patients S. Bosman1, F.A. Holman2, G.A.P. Nieuwenhuijzen1, H.J.T. Rutten1 1 Catharina Hospital, Surgery, Eindhoven, Netherlands 2 Leids University Medical Centre, Surgery, Leiden, Netherlands
ABSTRACTS 98. The effect of minimal invasive surgery on postoperative mortality in colorectal cancer surgery L. Gietelink1, M.W.J.M. Wouters2, R.A.E.M. Tollenaar1, P.J. Tanis3 1 Leiden University Medical Center, Surgery, Leiden, Netherlands 2 Netherlands Cancer Institute-Antoni van Leeuwenhoek, Surgery, Amsterdam, Netherlands 3 Academic Medical Center, Surgery, Amsterdam, Netherlands
Background: Surgical resection of local recurrent rectal cancer (LRRC) is often challenging. The anatomy is disturbed after prior surgery for the primary tumour. To achieve a radical resection, an extra anatomical resections is often required. These comprehensive procedures are often associated with increased blood loss and relatively high morbidity and mortality rates. It is unclear if it is safe to use intraoperative red blood cell salvage (ICS) in the treatment of patients with local recurrent rectal cancer. The objective of this study is to evaluate if the use of autologous blood through the cell saver is safe in patients with LRRC, regarding survival and complication rates. Material and methods: The Catharina hospital is a national referral centre for patients with recurrent rectal cancer. The Amount of blood products, the quantity of blood aspirated by the ICS and the blood volume returned to the patients was registered. Patient follow up was enrolled in a database; complications post-operative, presence of local recurrence, metastasis and overall survival was reported. Follow up ranged from 0 to 227 months, with a median of 40 months. Results: From 1994 until 2013, a total of 264 patients (mean age 63 year; 159 male, 105female) were treated with curative surgery. Patients were subdivided in two groups: patients who did or did not receive blood from the ICS. The mean blood loss was 6705cc (range 0-34000cc) of which 1533cc (range 72-6300cc) was returned with the ICS during surgery. The amount of blood loss was larger in the ICS group in contrast to patients in the non ICS group with an amount of blood loss >5L 65% vs 27%. More intra-abdominal abscesses occurred in the ICS group compared to the non ICS group (13% vs 2%), most likely due to the higher amount of blood loss in the ICS group. Multivariable analysis showed no influence of blood loss or blood products influencing the oncological outcome. The 5 year cancer specific, distant metastasis free, local recurrence free, relapse free and overall survival was 41, 49, 52, 33 and 35% respectively. The survival rates between the two groups did not differ significantly. Conclusions: The use of the cell saver in the treatment of patients with LRRC is safe and does not lead to additional complications. No disadvantageous effects were found concerning the oncological outcome, when comparing patients treated with the ICS and patients treated without the ICS. The use of the ICS should not be omitted because of fear for worse oncological outcome and should be implemented in the treatment of patients with LRRC. No conflict of interest.
Background: The use of minimal invasive surgery in colorectal cancer care has several potential benefits due to the causation of less surgical trauma. It potentially leads to a reduction of postoperative mortality, especially in high-risk patients. Meta-analyses, comparing laparoscopic to conventional surgery, showed a trend towards lower postoperative mortality, but were not able to show significant differences due to small sample sizes and relatively young and healthy study populations. Population studies, with a higher number of patients and events, did show significant reduction in casemix corrected postoperative mortality for minimal invasive surgery. The question remains whether selection bias (based on non measured casemix factors) were the cause of these results. As an alternative for casemix adjusted analyses, comparisons were made between elective open and laparoscopic resections in subgroups with similar operative risks as to minimalize this selection bias. Materials and methods: Data from the Dutch Surgical Colorectal Audit of 2010 to 2013 was used. All patients who underwent a resection for a primary colorectal tumor were analyzed. Subgroups with similar operative risks, based on age, ASA classification, tumor stage and previous abdominal surgery were formed and crude mortality rates were compared between laparoscopic and conventional surgery in each group. The influence of the laparoscopic approach on specific postoperative complications was analyzed in a univariate and multivariate model. Secondly, hospitals were divided into three tertiles according to their percentage of laparoscopic resections. Casemix corrected outcome measurements were calculated for all patients (laparoscopic/open surgery together) and compared between these tertiles. Results: For these analyses 35450 patients were included. Crude mortality rates were lower after laparoscopic resection in most subgroups. The highest absolute benefit was found for high-risk patients. Mortality rates after open and laparoscopic resection were 9.9 versus 6.7 percent respectively (p¼0.003) for patients with high operative risk. Furthermore, the laparoscopic approach was independently associated with a lower risk of cardiac (OR 0,66; 95%CI 0,58-0,74) and respiratory (OR 0,64; 95%CI 0,58-0,71) complications. Hospitals with a high percentage of laparoscopic resections showed an overall better performance on several casemix adjusted outcome parameters. Conclusions: These analyses convincingly show the positive influence of minimal invasive surgery on several postoperative outcomes. In most groups of patients the postoperative mortality was lower after a minimal invasive approach with the greatest advantage in groups with greater operative risk. Therefore it seems reasonable that, when both surgical techniques are possible, minimal invasive surgery has the preference over conventional surgery. No conflict of interest.
http://dx.doi.org/10.1016/j.ejso.2014.08.093
http://dx.doi.org/10.1016/j.ejso.2014.08.094