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Harries M.,Guys Hospital | Taylor A.,Uxbridge Business Park | Holmberg L.,King's College London | Agbaje O.,King's College London | And 3 more authors.
Cancer Epidemiology | Year: 2014

Background: Bone is the most common metastatic site associated with breast cancer. Using a database of women with breast cancer treated at Guy's Hospital, London 1976-2006 and followed until end 2010, we determined incidence of and survival after bone metastases. Methods: We calculated cumulative incidence of bone metastases considering death without prior bone metastases as a competing risk. Risk of bone metastases was modelled through Cox-regression. Survival after bone metastases diagnosis was calculated using Kaplan-Meier methodology. Results: Of the 7064 women, 589 (22%) developed bone metastases during 8.4 years (mean). Incidence of bone metastases was significantly higher in younger women, tumour size >5. cm, higher tumour grade, lobular carcinoma and ≥four positive nodes, but was not affected by hormone receptor status. Median survival after bone metastases diagnosis was 2.3 years in women with bone-only metastases compared with <1 year in women with visceral and bone metastases. There was a trend for decreased survival for patients who developed visceral metastases early, and proportionately fewer patients in this group. Interpretation: Incidence of bone metastases has decreased but bone metastases remain a highly relevant clinical problem due to the large number of patients being diagnosed with breast cancer. © 2014 Elsevier Ltd.

Rockberg J.,IMS Health | Bach B.A.,Amgen Inc. | Amelio J.,Uxbridge Business Park | Hernandez R.K.,Amgen Inc. | And 4 more authors.
The Journal of bone and joint surgery. American volume | Year: 2015

BACKGROUND: The Swedish Cancer Registry (founded in 1958) constitutes a unique resource for epidemiological studies of giant cell tumor of bone with potential for use for population-based studies of incidence over time. The aim of this study was to provide what we believe is the first modern population-based assessment of the incidence trends of giant cell tumor, a unique osteoclastogenic lytic stromal tumor with both benign and malignant histological forms, and to compare the findings with data from the same registry on osteosarcoma, a tumor that may display similar histological characteristics.METHODS: Cases were identified with use of codes for pathological bone tumor (International Classification of Diseases [ICD]-7 196). Specific morphological coding distinguishes benign (PAD 741) from malignant giant cell tumor (PAD 746) and osteosarcoma (PAD 766).RESULTS: During the period of 1958 to 2011, 4625 bone tumors were reported, including 505 giant cell tumors (383 benign and 122 malignant) and 1152 osteosarcomas. From 1958 to 1982 the ratio of malignant to benign giant cell tumors was 1.3, whereas from 1983 to 2011 the ratio inverted to 0.09, suggesting a change in the reporting or diagnosis of malignant or benign cases. Cases of giant cell tumor diagnosed from 1983 to 2011 displayed an age and sex distribution (median age at diagnosis, 34.0 years; 54% female) that were consistent with those in large published case series but differed from those in 1958 to 1982 (median age at diagnosis, 31.5 years; 48% female). The most current data (1983 to 2011) showed the giant cell tumor incidence in Sweden to be 1.3 per million per year, while the osteosarcoma incidence was 2.3 per million per year.CONCLUSIONS: Early Swedish Cancer Registry data (1958 to 1982) revealed a higher proportion of malignant giant cell tumors than seen in large sequential case series and a distinct age and sex profile compared with more recent data (1983 to 2011). This likely represents changes in the diagnostic workup and introduction of multidisciplinary review of giant-cell-containing tumors around 1982. Recent data may reflect the impact of expert centralized biopsy and multidisciplinary case review and more comprehensive reporting of benign giant cell tumors. Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.

Weycker D.,Policy Analysis Inc. PAI | Danel A.,Amgen | Marciniak A.,Uxbridge Business Park | Bendall K.,Cascade | And 2 more authors.
BMC Cancer | Year: 2012

Background: Economic implications of chemotherapy-induced febrile neutropenia (FN) in European and Australian clinical practice are largely unknown.Methods: Data were obtained from a European (97%) and Australian (3%) observational study of patients with non-Hodgkin's lymphoma (NHL) receiving CHOP (±rituximab) chemotherapy. For each patient, each cycle of chemotherapy within the course, and each occurrence of FN within cycles, was identified. Patients developing FN in a given cycle (" FN patients" ), starting with the first, were matched to those who did not develop FN in that cycle (" comparison patients" ), irrespective of subsequent FN events. FN-related healthcare costs (£2010) were tallied for the initial FN event as well as follow-on care and FN events in subsequent cycles.Results: Mean total cost was £5776 (95%CI £4928-£6713) higher for FN patients (n = 295) versus comparison patients, comprising £4051 (£3633-£4485) for the initial event and a difference of £1725 (£978-£2498) in subsequent cycles. Among FN patients requiring inpatient care (76% of all FN patients), mean total cost was higher by £7259 (£6327-£8205), comprising £5281 (£4810-£5774) for the initial hospitalization and a difference of £1978 (£1262-£2801) in subsequent cycles.Conclusions: Cost of chemotherapy-induced FN among NHL patients in European and Australian clinical practice is substantial; a sizable percentage is attributable to follow-on care and subsequent FN events. © 2012 Weycker et al.; licensee BioMed Central Ltd.

PubMed | Uxbridge Business Park, Amgen and Niguarda Cancer Center
Type: Journal Article | Journal: Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation | Year: 2016

Epidermal growth factor receptor inhibitors such as panitumumab are associated with characteristic skin toxicities. We summarise data from three panitumumab clinical trials to investigate the potential impact of skin toxicity on quality of life (QoL) in patients with metastatic colorectal cancer (mCRC).The studies were randomised, open-label trials comparing standard treatment (first-line FOLFOX4 [n=456], second-line FOLFIRI [n=381], or best supportive care [n=114]) with or without panitumumab in adults with KRAS/NRAS (RAS) wild-type mCRC. QoL was assessed using the EuroQoL 5-domain health state index (HSI) and overall health rating (OHR) measures. Impact of skin toxicity on changes in QoL scores was estimated using a linear mixed-effects model. Worst skin toxicity was defined in separate models as a subgroup variable or as a measure over time.Regardless of analysis method, there were no statistically significant differences between the panitumumab and comparator arms in any of the studies in terms of change in HSI or OHR scores. There were no statistically significant differences in QoL outcomes between patients with worst skin toxicity grade <3 and those with grade 3. In addition, there were no statistically significant differences between the panitumumab and comparator arms in subgroups of patients with worst skin toxicity of grade <3 and 3.Addition of panitumumab to chemotherapy in RAS wild-type mCRC has no statistically significant negative effect on overall QoL, despite skin toxicity. Skin toxicity of worst grade 3 appeared to have similar impact on QoL as skin toxicity of grade <3.

Yong M.,Amgen Inc. | Schoonen W.M.,Uxbridge Business Park | Li L.,Boston University | Kanas G.,Exponent, Inc. | And 5 more authors.
British Journal of Haematology | Year: 2010

This study assessed the incidence of immune thrombocytopenia (ITP) and characteristics associated with ITP in the paediatric population using the General Practice Research Database (GPRD). Two hundred and fifty-seven paediatric ITP patients were identified out of 1145 incident patients with ITP recorded between 1990 and 2005. The age-specific incidence for ITP in paediatric patients was 4·2 per 100 000 person-years (PY) [95% confidence interval (CI): 3·7-4·8 per 100 000 PY], with a statistically significantly higher incidence in boys compared to girls aged 2-5 years [9·7 (95% CI: 7·5-12·2) per 100 000 PY vs. 4·7 (95% CI: 3·2-6·6) per 100 000 PY, respectively]. By contrast, among teenagers aged 13-17 years, the overall incidence was lower [2·4 (95% CI: 1·7-3·3) per 100 000 PY] with a similar incidence in girls and boys. There was a relationship between age and sex with ITP incidence, suggesting that patterns of disease burden differ among children and teenagers. Evidence of an infection or immunization shortly before ITP diagnosis was apparent in 52 (20·2%) and 22 (8·6%) of the 257 paediatric ITP patients, respectively. Two deaths were observed during the study period. ITP is an important although rarely fatal disease in paediatric patients and its aetiology remains unexplained in the majority of cases. © 2010 Blackwell Publishing Ltd.

Hagberg K.W.,Boston University | Taylor A.,Uxbridge Business Park | Hernandez R.K.,Amgen Inc. | Jick S.,Boston University
Cancer Epidemiology | Year: 2013

Background: Bone is a frequent site for metastases among women with breast cancer. We conducted a study using the General Practice Research Database (GPRD), with linkage to the National Cancer Registry (NCR) and Hospital Episode Statistics (HES), to estimate the incidence of bone metastases in women with breast cancer in the United Kingdom. Methods: We identified all women in the GPRD aged 20-99 with a first-time diagnosis of breast cancer between 2000 and 2006. To address potential underreporting, we developed and validated an algorithm to serve as a proxy for bone metastases. Bone metastases were defined as (1) a bone cancer diagnosis code on the same day or following breast cancer diagnosis date, or (2) another metastasis code plus codes consistent with bone metastases diagnosis or treatment using the algorithm. We sent questionnaires to a sample of general practitioners to validate these definitions. Results: We included 13,207 breast cancer patients (median age at diagnosis of 61 years) who contributed 70,885 person-years of follow-up. The majority of patients had stage 1 or 2 breast cancer (90.4%), and 2.6% had metastatic breast cancer at diagnosis. We identified 788 women (6.0%) with bone metastases after a median follow-up of 5.4 years. Questionnaire results validated the diagnosis of bone metastases in 88% of patients with a bone cancer code and for 70% identified with the algorithm. Conclusion: This is the first time the GPRD has been linked to HES and NCR to study the epidemiology of bone metastases, adding important information on the burden of bone metastasis. © 2013 Elsevier Ltd.

Katz A.J.,Amgen Inc. | Chia V.M.,Amgen Inc. | Schoonen W.M.,Uxbridge Business Park | Kelsh M.A.,Amgen Inc.
Cancer Causes and Control | Year: 2015

Purpose: Acute lymphoblastic leukemia (ALL) is a rare hematological malignancy. With the recent introduction of a classification system for hematopoietic and lymphoid neoplasms, more comprehensive assessment of ALL epidemiology is now possible. In this study, we describe recent international incidence of ALL and project the annual number of diagnoses to 2025. We also estimate relative survival and average potential years of life lost (AYLL) to assess the societal burden of ALL. Methods: Age-specific incidence data for ALL from select cancer registries in different geographies were obtained from the International Agency for Research on Cancer’s Cancer Incidence in Five Continents Database. Country-specific age-standardized rates were calculated to allow for direct comparisons between countries. ALL-specific mortality and relative survival data were only available from the United States (US) National Cancer Institute’s Surveillance, Epidemiology, and End Results program; mortality rates were estimated for other countries. Results: The age-standardized incidence rate of ALL during 2003–2007 ranged from 1.08 to 2.12 per 100,000 person-years in selected countries. Incidence was generally higher in the Americas and Oceania and lower in Asia and Eastern Europe. In most countries, the incidence rate of ALL in children was approximately four times that in adults. Survival was particularly poor among adults. In selected countries, the estimated AYLL ranged from 30 to 48 years for all ages and from 23 to 39 years for adults. Conclusions: Although a rare disease, ALL presents a significant public health burden given poor survival outcomes among adults, AYLL, and its importance as the most common pediatric cancer. © 2015, Springer International Publishing Switzerland.

Green J.,University of Oxford | Roddam A.,University of Oxford | Roddam A.,Uxbridge Business Park | Pirie K.,University of Oxford | And 3 more authors.
British Journal of Cancer | Year: 2012

Background: Hormonal factors may influence risk for upper gastrointestinal cancers in women. We examined risk of oesophageal and gastric cancers in relation to reproductive factors in a large UK cohort, the Million Women Study. Methods: Among 1 319 409 women aged on average 56 years at recruitment, 1186 incident cancers of the oesophagus and 1194 of the stomach were registered during 11.9 million person-years observation. Adjusted relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. Results: Risks of both oesophageal and gastric cancer were significantly higher in postmenopausal than in pre-or peri-menopausal women (RRs 1.46, 1.07-2.00 and 1.59, 1.15-2.20, respectively; P≤0.01 for both); and, among postmenopausal women, risk was higher the younger women were at menopause (RR, 95% CI per 5 years younger at menopause 1.18, 1.05-1.34 for oesophageal cancer and 1.18, 1.04-1.34 for stomach cancer, P trend= 0.01 for both). For factors relating to childbearing, including women's age at first birth, their number of children, and breastfeeding history, the only significant association was a higher risk of oesophageal cancer in nulliparous, compared with parous, women (RR 1.31, 1.11-1.55; P=0.002). When risks for squamous cell and adenocarcinomas of the oesophagus were compared, most did not differ significantly, but statistical power was limited. Conclusion: Both oesophageal and gastric cancer risks appeared to be related to menopausal status and age at menopause, but there was little consistent evidence for associations with factors related to childbearing. © 2012 Cancer Research UK All rights reserved.

PubMed | Amgen Inc. and Uxbridge Business Park
Type: Journal Article | Journal: International journal of hematology | Year: 2016

This meta-analysis describes the incidence rate of arterial and venous thromboembolism (ATE and VTE) in patients with immune thrombocytopenia (ITP), and the relative risk of ATE and VTE in patients with ITP and comparable populations without ITP. MEDLINE and EMBASE were systematically searched for observational studies reporting incidence rates of ATE and VTE in populations with and without ITP between 1996 and 2013 [follow-up completed before thrombopoietin receptor (TPOr) agonists were commercially available]. Three large, population-based studies were identified from Denmark, the United Kingdom, and the United States. The incidence of ATE per 100 patient-years among patients with ITP ranged from 1.0 to 2.8, and among populations without ITP ranged from 0.7 to 1.8; the summary relative risk adjusted for matching factors (aRR) was 1.5 [95% confidence interval (CI) 1.3, 1.8]. The incidence of VTE per 100 patient-years among patients with ITP ranged from 0.4 to 0.7, and among populations without ITP ranged from 0.1 to 0.4; the summary aRR (95% CI) was 1.9 (1.4, 2.7). The risk of ATE and VTE among patients with ITP, based on evidence from three large, population-based observational studies, should be considered when evaluating the risk of thromboembolism attributed to ITP treatments, such as TPOr agonists.

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