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Robertson C.,University of Aberdeen | Arcot Ragupathy S.K.,Royal Infirmary | Boachie C.,University of Aberdeen | Dixon J.M.,Edinburgh Breast Unit | And 19 more authors.
Health Technology Assessment

Background: Following primary breast cancer treatment, the early detection of ipsilateral breast tumour recurrence (IBTR) or ipsilateral secondary cancer in the treated breast and detection of new primary cancers in the contralateral breast is beneficial for survival. Surveillance mammography is used to detect these cancers, but the optimal frequency of surveillance and the length of follow-up are unclear. Objectives: To identify feasible management strategies for surveillance and follow-up of women after treatment for primary breast cancer in a UK setting, and to determine the effectiveness and cost-effectiveness of differing regimens. Methods: A survey of UK breast surgeons and radiologists to identify current surveillance mammography regimens and inform feasible alternatives; two discrete systematic reviews of evidence published from 1990 to mid 2009 to determine (i) the clinical effectiveness and cost-effectiveness of differing surveillance mammography regimens for patient health outcomes and (ii) the test performance of surveillance mammography in the detection of IBTR and metachronous contralateral breast cancer (MCBC); statistical analysis of individual patient data (West Midlands Cancer Intelligence Unit Breast Cancer Registry and Edinburgh data sets); and economic modelling using the systematic reviews results, existing data sets, and focused searches for specific data analysis to determine the effectiveness and cost-utility of differing surveillance regimens. Results: The majority of survey respondents initiate surveillance mammography 12 months after breast-conserving surgery (BCS) (87%) or mastectomy (79%). Annual surveillance mammography was most commonly reported for women after BCS or after mastectomy (72% and 53%, respectively). Most (74%) discharge women from surveillance mammography, most frequently 10 years after surgery. The majority (82%) discharge from clinical follow-up, most frequently at 5 years. Combining initiation, frequency and duration of surveillance mammography resulted in 54 differing surveillance regimens for women after BCS and 56 for women following mastectomy. The eight studies included in the clinical effectiveness systematic review suggest surveillance mammography offers a survival benefit compared with a surveillance regimen that does not include surveillance mammography. Nine studies were included in the test performance systematic review. For routine IBTR detection, surveillance mammography sensitivity ranged from 64% to 67% and specificity ranged from 85% to 97%. For magnetic resonance imaging (MRI), sensitivity ranged from 86% to 100% and specificity was 93%. For non-routine IBTR detection, sensitivity and specificity for surveillance mammography ranged from 50% to 83% and from 57% to 75%, respectively, and for MRI from 93% to 100% and from 88% to 96%, respectively. For routine MCBC detection, one study reported sensitivity of 67% and specificity of 50% for both surveillance mammography and MRI, although this was a highly select population. Data set analysis showed that IBTR has an adverse effect on survival. Furthermore, women experiencing a second tumour measuring > 20 mm in diameter were at a significantly greater risk of death than those with no recurrence or those whose tumour was < 10 mm in diameter. In the base-case analysis, the strategy with the highest net benefit, and most likely to be considered cost-effective, was surveillance mammography alone, provided every 12 months at a societal willingness to pay for a quality-adjusted lifeyear of either £20,000 or £30,000. The incremental cost-effectiveness ratio for surveillance mammography alone every 12 months compared with no surveillance was £4727. Limitations: Few studies met the review inclusion criteria and none of the studies was a randomised controlled trial. The limited and variable nature of the data available precluded any quantitative analysis. There was no useable evidence contained in the Breast Cancer Registry database to assess the effectiveness of surveillance mammography directly. The results of the economic model should be considered exploratory and interpreted with caution given the paucity of data available to inform the economic model. Conclusions: Surveillance is likely to improve survival and patients should gain maximum benefit through optimal use of resources, with those women with a greater likelihood of developing IBTR or MCBC being offered more comprehensive and more frequent surveillance. Further evidence is required to make a robust and informed judgement on the effectiveness of surveillance mammography and follow-up. The utility of national data sets could be improved and there is a need for high-quality, direct head-to-head studies comparing the diagnostic accuracy of tests used in the surveillance population. Funding: The National Institute for Health Research Health Technology Assessment programme. © Queen's Printer and Controller of HMSO 2011. Source

Walters S.,London School of Hygiene and Tropical Medicine | Maringe C.,London School of Hygiene and Tropical Medicine | Butler J.,Royal Marsden Hospital | Rachet B.,London School of Hygiene and Tropical Medicine | And 19 more authors.
British Journal of Cancer

Background: We investigate whether differences in breast cancer survival in six high-income countries can be explained by differences in stage at diagnosis using routine data from population-based cancer registries. Methods: We analysed the data on 257 362 women diagnosed with breast cancer during 2000-7 and registered in 13 population-based cancer registries in Australia, Canada, Denmark, Norway, Sweden and the UK. Flexible parametric hazard models were used to estimate net survival and the excess hazard of dying from breast cancer up to 3 years after diagnosis.Results:Age-standardised 3-year net survival was 87-89% in the UK and Denmark, and 91-94% in the other four countries. Stage at diagnosis was relatively advanced in Denmark: only 30% of women had Tumour, Nodes, Metastasis (TNM) stage I disease, compared with 42-45% elsewhere. Women in the UK had low survival for TNM stage III-IV disease compared with other countries. Conclusion: International differences in breast cancer survival are partly explained by differences in stage at diagnosis, and partly by differences in stage-specific survival. Low overall survival arises if the stage distribution is adverse (e.g. Denmark) but stage-specific survival is normal; or if the stage distribution is typical but stage-specific survival is low (e.g. UK). International differences in staging diagnostics and stage-specific cancer therapies should be investigated. © 2013 Cancer Research UK. All rights reserved. Source

Coleman M.P.,London School of Hygiene and Tropical Medicine | Forman D.,International Agency for Research on Cancer | Bryant H.,Canadian Partnership Against Cancer | Rachet B.,London School of Hygiene and Tropical Medicine | And 19 more authors.
The Lancet

Cancer survival is a key measure of the effectiveness of health-care systems. Persistent regional and international differences in survival represent many avoidable deaths. Differences in survival have prompted or guided cancer control strategies. This is the first study in a programme to investigate international survival disparities, with the aim of informing health policy to raise standards and reduce inequalities in survival. Data from population-based cancer registries in 12 jurisdictions in six countries were provided for 2·4 million adults diagnosed with primary colorectal, lung, breast (women), or ovarian cancer during 1995-2007, with follow-up to Dec 31, 2007. Data quality control and analyses were done centrally with a common protocol, overseen by external experts. We estimated 1-year and 5-year relative survival, constructing 252 complete life tables to control for background mortality by age, sex, and calendar year. We report age-specific and age-standardised relative survival at 1 and 5 years, and 5-year survival conditional on survival to the first anniversary of diagnosis. We also examined incidence and mortality trends during 1985-2005. Relative survival improved during 1995-2007 for all four cancers in all jurisdictions. Survival was persistently higher in Australia, Canada, and Sweden, intermediate in Norway, and lower in Denmark, England, Northern Ireland, and Wales, particularly in the first year after diagnosis and for patients aged 65 years and older. International differences narrowed at all ages for breast cancer, from about 9 to 5 at 1 year and from about 14 to 8 at 5 years, but less or not at all for the other cancers. For colorectal cancer, the international range narrowed only for patients aged 65 years and older, by 2-6 at 1 year and by 2-3 at 5 years. Up-to-date survival trends show increases but persistent differences between countries. Trends in cancer incidence and mortality are broadly consistent with these trends in survival. Data quality and changes in classification are not likely explanations. The patterns are consistent with later diagnosis or differences in treatment, particularly in Denmark and the UK, and in patients aged 65 years and older. Department of Health, England; and Cancer Research UK. © 2011 Elsevier Ltd. Source

Lepage C.,University of Burgundy | Ciccolallo L.,Fondazione Istituto Nazionale Dei Tumori | De Angelis R.,Istituto Superiore di Sanita | De Angelis R.,Centro Nazionale Of Epidemiologia | And 63 more authors.
International Journal of Cancer

The aim of this study was to report on malignant digestive endocrine tumours (MDET) prognosis in several European countries. We analysed survival data from 19 cancer registries in 12 European countries on 3,715 MDET diagnosed between 1985 and 1994. The overall 5-year survival rate was 47.5%. It was 58.1% for differentiated MDET and 8.1% for small-cell MDET (p < 0.001), 55.9% for patients under 65 and 37.0% for older patients. Survival rates for small intestinal and colorectal were higher than for the other sites. The 5-year relative survival rates were 60.3% in Northern Europe, 53.6% in Western Continental Europe, 42.5% in the UK, 37.6% in Eastern Europe (p < 0.001). Among well-differentiated pancreatic tumours, 5-year relative survival was 55.6% for insulinoma, 48.4% for gastrinoma, 33.4% for glucagonoma, 28.8% for carcinoïd tumours and 49.9% for non-functioning tumours. The relative excess risk of death was significantly lower in Western Continental Europe and Northern Europe and significantly higher in Easter European compared to the UK. MDET differentiation, site, geographic area, age and sex, were independent prognostic factors. Overall, in Europe approximately half of the patients with MDET survive 5 years after the initial diagnosis. Prognosis varies with tumour differentiation, anatomic site and histological type. There are significant differences in survival from MDET among European countries, independently of other prognostic factors. Source

Moss E.L.,Royal Infirmary | Moss E.L.,West Midlands Cancer Intelligence Unit | Evans T.,West Midlands Cancer Intelligence Unit | Pearmain P.,West Midlands Cancer Intelligence Unit | And 5 more authors.
International Journal of Gynecological Cancer

Introduction The dualistic theory of ovarian carcinogenesis proposes that epithelial "ovarian" cancer is not one entity with several histological subtypes but a collection of different diseases arising from cells of different origin, some of which may not originate in the ovarian surface epithelium. Methods All cases referred to the Pan-Birmingham Gynaecological Cancer Centre with an ovarian, tubal, or primary peritoneal cancer between April 2006 and April 2012 were identified from the West Midlands Cancer Registry. Tumors were classified into type I (low-grade endometrioid, clear cell, mucinous, and low-grade serous) and type II (high-grade serous, high-grade endometrioid, carcinosarcoma, and undifferentiated) cancers. Results Ovarian (83.5%), tubal (4.3%), or primary peritoneal carcinoma (12.2%) were diagnosed in a total of 583 woman. The ovarian tumors were type I in 134 cases (27.5%), type II in 325 cases (66.7%), and contained elements of both type I and type II tumors in 28 cases (5.7%). Most tubal and primary peritoneal cases, however, were type II tumors: 24 (96.0%) and 64 (90.1%), respectively. Only 16 (5.8%) of the ovarian high-grade serous carcinomas were stage I at diagnosis, whereas 240 (86.6%) were stage III+. Overall survival varied between the subtypes when matched for stage. Stage III low-grade serous and high-grade serous carcinomas had a significantly better survival compared to clear cell and mucinous cases, P = 0.0134. There was no significant difference in overall survival between the high-grade serous ovarian, tubal, or peritoneal carcinomas when matched for stage (stage III, P = 0.3758; stage IV, P = 0.4820). Conclusions Type II tumors are more common than type I and account for most tubal and peritoneal cancers. High-grade serous carcinomas, whether classified as ovarian/tubal/peritoneal, seem to behave as one disease entity with no significant difference in survival outcomes, therefore supporting the proposition of a separate classification of "tubo-ovarian serous carcinoma". © 2015 by IGCS and ESGO. Source

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