- Email: [email protected]
Surgery improves survival in women over 75 years with breast cancer
1206 21. Breast conserving surgery: are reoperation rates too high? Analyses of a linked HES-Cancer Registry dataset Ranjeet Jeevana, G. Lawrenceb, M. Trivellaa, S. Charmana, O. Kearinsb, D. Cromwella, J. van der Meulena a The Royal College of Surgeons of England, 35-43 Lincoln’s Inn Fields, London, WC2A 3PE b West Midlands Cancer Intelligence Unit
Introduction: Breast conserving surgery (BCS) is often used to treat women with invasive breast cancer or carcinoma in situ (CIS). In 2009, the ABS set a quality of care target: no women undergoing BCS should require more than three operations in total. Methods: Reoperation rates following primary BCS (OPCS-4 B28) for invasive carcinoma (ICD-10 C50) and CIS (ICD-10 D05) were calculated using linked Hospital Episode Statistics (1997-2007) and Cancer Registry data (1996-2004). Reoperation was defined as further BCS or a mastectomy (OPCS-4 B27) within six months of the primary surgery. Results: In the English NHS, 224,713 women underwent BCS as their first surgical treatment between 1997 and 2007. In the following six months, 183,955 (81.9%) underwent no further resection of the breast. 36,826 (16.4%) required one further operation to the breast, of which 18,499 (50.2%) involved BCS and 18,327 (49.8%) a mastectomy. 1,064 (0.5%) women underwent two or more BCS reoperations without subsequent mastectomy, while the remaining 2,868 (1.3%) had one or more BCS reoperations before proceeding to mastectomy. Conclusion: Almost one in five women requires further resection of the breast after primary BCS. The national reoperation rate appears to meet the ABS minimum standards (3 or fewer operations for 95% of patients). However, these analyses do not take into account the increasing number of axillary reoperations following sentinel node biopsy. We hope that this type of reporting will inform both pre-operative planning and patient decision-making, and in doing so help to reduce the BCS reoperation rate in England. 22. Efficacy of the specific ETA receptor antagonist zibotentan in colorectal cancer cells and colorectal fibroblasts Samer-ul Haque, M. Heetun, I. Taylor, X. Shiwen, M. Winslet, M. Loizidou UCL Medical School, Dept. of Surgery, Royal Free Campus, Pond Street, Hampstead, London, NW3 2QG
Introduction: Endothelin-1 (ET-1) contributes to growth and progression of solid cancers, mainly through endothelin receptor A (ETAR). Therefore ET receptor antagonism is emerging as a potential treatment for neoplasms. We evaluated the efficacy of the specific ETAR antagonist zibotentan (ZD4054) in blocking ET-driven cellular effects in colorectal cancer (CRC). Methods: CRC cell lines (HT29, SW620) and primary normal fibroblast strains isolated from human colorectal tissues (CF36;CF56;CF65;CF75) were incubated in ET-1 with/without BQ123, zibotentan (ETAR antagonists), BQ788 (ETBR antagonist). Resultant cell growth was measured by the colourimetric methylene blue assay; migration by a monolayer scratch assay; contraction in collagen gels; downstream effectors by western blotting. Results: ET-1 driven growth (18%-45% above control) was significantly inhibited (p < 0.01, 1-way ANOVA, Tukeys post-hoc analysis) by ETAR (not ETBR) antagonism (BQ123¼zibotentan; CRC and fibroblasts). ET-1 driven fibroblast migration and contraction were blocked by ETAR and ETBR antagonism (zibotentan ¼ BQ123). CRC cells did not migrate or contract. ET-1stimulated expression of downstream effectors was driven by ETAR or ETBR, eg: (1) connective tissue growth factor was blocked by ETAR antagonism (zibotentan > BQ123; CRC and fibroblasts); (2) collagen XI was blocked by ETAR > ETBR antagonism (zibotentan > BQ123; fibroblasts). Conclusions: The specific ETAR antagonist zibotentan is at least as efficacious as BQ123 in blocking ET-1 driven growth, migration and contraction both in CRC cells and colorectal fibroblasts, which form the supporting tumour stroma. Zibotentan is a strong candidate for adjuvant treatment in CRC.
ABSTRACTS 23. Surgery improves survival in women over 75 years with breast cancer Chinedu Chianakwalam, V. Stevenson William Harvey Hospital, Kennington Road, Ashford, Kent, TN24 0LZ
Introduction: The optimal management of elderly patients with breast cancer remains controversial. The aim of this study is to review the survival of women over the age of 75 following treatment for breast cancer. Methods: The database was reviewed for women 75 years and older at diagnosis with breast cancer between January 1996 and December 2005 and their treatment recorded. The 5-year overall survival (OS) and breast cancer specific survival (BCSS) were compared between those that had surgery (S) and no surgery (NS) using the Kaplan-Meier and Cox regression methods. Results: There were 354 patients with a median age of 80 years (range 75e98). Of 161 (46%) patients with (NS), 158 received endocrine treatment (ET) only, 1 had radiotherapy (RT) only and 8 had RT and ET. 193 (54%) patients had (S). Of 92 treated with breast conserving surgery, 76 had axillary lymph node dissection (ALND) and 63 received adjuvant RT. 101 patients had a mastectomy - 88 with ALND while 13 had chest wall RT. No patient received chemotherapy. 5-year OS was (NS (23%) vs S (66%) Log rank P < 0.0001) and BCSS (NS (43%) vs S (92%) Log rank P < 0.0001). On multivariate analysis surgery was an independent risk factor for OS and BCSS. Conclusions: Surgery is an independent positive risk factor and significantly improves both overall and breast cancer specific survival in women over 75 years. 24. Extended lymphadenectomy vs conventional surgery for rectal cancer: a meta-analysis Panagiotis Georgioua, E. Tanb, R. Nichollsb, A. Antonioua, G. Brownc, P. Tekkisa a Department of Colorectal Surgery, The Royal Marsden Hospital, Fulham Road, London, SW3 6JJ b Academic Surgery, Chelsea and Westminster Campus, Imperial College, London c Department of Radiology, The Royal Marsden Hospital
Introduction: Lateral pelvic lymph node metastases occur in 10-25% of patients with rectal cancer and are associated with higher local recurrence and reduced survival rates. The present study examined the value of extended lateral pelvic lymphadenectomy in the operative management of rectal cancer. Methods: Published trials between 1984 and 2007 comparing extended lymphadenectomy (EL) versus non-extended lymphadenectomy (non-EL) for rectal cancer, were included. End-points evaluated were perioperative outcomes, survival and recurrence rates. A random effects meta-analytical model was used and between-study heterogeneity assessed. Results: Twenty-one studies evaluating 6042 patients were analysed; 2974 patients underwent EL and 3068 non-EL. Operative time was significantly longer in the EL group by 102.56 mins; p < 0.001. Intra-operative blood loss was greater in the EL group by 594.01 mls, p < 0.001. Although post-operative mortality and morbidity were similar between the two groups, urinary dysfunction was higher in the EL group (p ¼ 0.004). Male sexual dysfunction was also more prevalent in the EL group. There were no significant differences in terms of 5-year survival (OR ¼ 0.95, p ¼ 0.89), 5-year disease-free survival (OR ¼ 0.95, p ¼ 0.89), local (OR ¼ 0.96, p ¼ 0.69) or distant recurrence (OR ¼ 1.11, p ¼ 0.06). Sensitivity analysis revealed an advantage in favour of the non-EL group, in terms of local recurrence, without any other changes in the significance of the rest of the outcomes. Conclusion: Extended lymphadenectomy is associated with increased sexual and urinary dysfunction and does not appear to confer a significant cancer specific advantage. It may have a role though, in a selected group of patients with more advanced disease.
Introduction: Breast conserving surgery (BCS) is often used to treat women with invasive breast cancer or carcinoma in situ (CIS). In 2009, the ABS set a quality of care target: no women undergoing BCS should require more than three operations in total. Methods: Reoperation rates following primary BCS (OPCS-4 B28) for invasive carcinoma (ICD-10 C50) and CIS (ICD-10 D05) were calculated using linked Hospital Episode Statistics (1997-2007) and Cancer Registry data (1996-2004). Reoperation was defined as further BCS or a mastectomy (OPCS-4 B27) within six months of the primary surgery. Results: In the English NHS, 224,713 women underwent BCS as their first surgical treatment between 1997 and 2007. In the following six months, 183,955 (81.9%) underwent no further resection of the breast. 36,826 (16.4%) required one further operation to the breast, of which 18,499 (50.2%) involved BCS and 18,327 (49.8%) a mastectomy. 1,064 (0.5%) women underwent two or more BCS reoperations without subsequent mastectomy, while the remaining 2,868 (1.3%) had one or more BCS reoperations before proceeding to mastectomy. Conclusion: Almost one in five women requires further resection of the breast after primary BCS. The national reoperation rate appears to meet the ABS minimum standards (3 or fewer operations for 95% of patients). However, these analyses do not take into account the increasing number of axillary reoperations following sentinel node biopsy. We hope that this type of reporting will inform both pre-operative planning and patient decision-making, and in doing so help to reduce the BCS reoperation rate in England. 22. Efficacy of the specific ETA receptor antagonist zibotentan in colorectal cancer cells and colorectal fibroblasts Samer-ul Haque, M. Heetun, I. Taylor, X. Shiwen, M. Winslet, M. Loizidou UCL Medical School, Dept. of Surgery, Royal Free Campus, Pond Street, Hampstead, London, NW3 2QG
Introduction: Endothelin-1 (ET-1) contributes to growth and progression of solid cancers, mainly through endothelin receptor A (ETAR). Therefore ET receptor antagonism is emerging as a potential treatment for neoplasms. We evaluated the efficacy of the specific ETAR antagonist zibotentan (ZD4054) in blocking ET-driven cellular effects in colorectal cancer (CRC). Methods: CRC cell lines (HT29, SW620) and primary normal fibroblast strains isolated from human colorectal tissues (CF36;CF56;CF65;CF75) were incubated in ET-1 with/without BQ123, zibotentan (ETAR antagonists), BQ788 (ETBR antagonist). Resultant cell growth was measured by the colourimetric methylene blue assay; migration by a monolayer scratch assay; contraction in collagen gels; downstream effectors by western blotting. Results: ET-1 driven growth (18%-45% above control) was significantly inhibited (p < 0.01, 1-way ANOVA, Tukeys post-hoc analysis) by ETAR (not ETBR) antagonism (BQ123¼zibotentan; CRC and fibroblasts). ET-1 driven fibroblast migration and contraction were blocked by ETAR and ETBR antagonism (zibotentan ¼ BQ123). CRC cells did not migrate or contract. ET-1stimulated expression of downstream effectors was driven by ETAR or ETBR, eg: (1) connective tissue growth factor was blocked by ETAR antagonism (zibotentan > BQ123; CRC and fibroblasts); (2) collagen XI was blocked by ETAR > ETBR antagonism (zibotentan > BQ123; fibroblasts). Conclusions: The specific ETAR antagonist zibotentan is at least as efficacious as BQ123 in blocking ET-1 driven growth, migration and contraction both in CRC cells and colorectal fibroblasts, which form the supporting tumour stroma. Zibotentan is a strong candidate for adjuvant treatment in CRC.
ABSTRACTS 23. Surgery improves survival in women over 75 years with breast cancer Chinedu Chianakwalam, V. Stevenson William Harvey Hospital, Kennington Road, Ashford, Kent, TN24 0LZ
Introduction: The optimal management of elderly patients with breast cancer remains controversial. The aim of this study is to review the survival of women over the age of 75 following treatment for breast cancer. Methods: The database was reviewed for women 75 years and older at diagnosis with breast cancer between January 1996 and December 2005 and their treatment recorded. The 5-year overall survival (OS) and breast cancer specific survival (BCSS) were compared between those that had surgery (S) and no surgery (NS) using the Kaplan-Meier and Cox regression methods. Results: There were 354 patients with a median age of 80 years (range 75e98). Of 161 (46%) patients with (NS), 158 received endocrine treatment (ET) only, 1 had radiotherapy (RT) only and 8 had RT and ET. 193 (54%) patients had (S). Of 92 treated with breast conserving surgery, 76 had axillary lymph node dissection (ALND) and 63 received adjuvant RT. 101 patients had a mastectomy - 88 with ALND while 13 had chest wall RT. No patient received chemotherapy. 5-year OS was (NS (23%) vs S (66%) Log rank P < 0.0001) and BCSS (NS (43%) vs S (92%) Log rank P < 0.0001). On multivariate analysis surgery was an independent risk factor for OS and BCSS. Conclusions: Surgery is an independent positive risk factor and significantly improves both overall and breast cancer specific survival in women over 75 years. 24. Extended lymphadenectomy vs conventional surgery for rectal cancer: a meta-analysis Panagiotis Georgioua, E. Tanb, R. Nichollsb, A. Antonioua, G. Brownc, P. Tekkisa a Department of Colorectal Surgery, The Royal Marsden Hospital, Fulham Road, London, SW3 6JJ b Academic Surgery, Chelsea and Westminster Campus, Imperial College, London c Department of Radiology, The Royal Marsden Hospital
Introduction: Lateral pelvic lymph node metastases occur in 10-25% of patients with rectal cancer and are associated with higher local recurrence and reduced survival rates. The present study examined the value of extended lateral pelvic lymphadenectomy in the operative management of rectal cancer. Methods: Published trials between 1984 and 2007 comparing extended lymphadenectomy (EL) versus non-extended lymphadenectomy (non-EL) for rectal cancer, were included. End-points evaluated were perioperative outcomes, survival and recurrence rates. A random effects meta-analytical model was used and between-study heterogeneity assessed. Results: Twenty-one studies evaluating 6042 patients were analysed; 2974 patients underwent EL and 3068 non-EL. Operative time was significantly longer in the EL group by 102.56 mins; p < 0.001. Intra-operative blood loss was greater in the EL group by 594.01 mls, p < 0.001. Although post-operative mortality and morbidity were similar between the two groups, urinary dysfunction was higher in the EL group (p ¼ 0.004). Male sexual dysfunction was also more prevalent in the EL group. There were no significant differences in terms of 5-year survival (OR ¼ 0.95, p ¼ 0.89), 5-year disease-free survival (OR ¼ 0.95, p ¼ 0.89), local (OR ¼ 0.96, p ¼ 0.69) or distant recurrence (OR ¼ 1.11, p ¼ 0.06). Sensitivity analysis revealed an advantage in favour of the non-EL group, in terms of local recurrence, without any other changes in the significance of the rest of the outcomes. Conclusion: Extended lymphadenectomy is associated with increased sexual and urinary dysfunction and does not appear to confer a significant cancer specific advantage. It may have a role though, in a selected group of patients with more advanced disease.