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1.
Breast Cancer Res Treat ; 180(3): 809-817, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32170635

RESUMO

BACKGROUND: Genomic tests are increasingly being used by clinicians when considering adjuvant chemotherapy for patients with oestrogen receptor-positive (ER+), human epidermal growth factor 2-negative (HER2-) breast cancer. The Oncotype DX breast recurrence score assay was the first test available in the UK National Health Service. This study looked at how UK clinicians were interpreting Recurrence Scores (RS) in everyday practice. METHODS: RS, patient and tumour characteristics and adjuvant therapy details were retrospectively collected for 713 patients from 14 UK cancer centres. Risk by RS-pathology-clinical (RSPC) was calculated and compared to the low/intermediate/risk categories, both as originally defined (RS < 18, 18-30 and > 30) and also using redefined boundaries (RS < 11, 11-25 and > 25). RESULTS: 49.8%, 36.2% and 14% of patients were at low (RS < 18), intermediate (RS 18-30) and high (RS > 30) risk of recurrence, respectively. Overall 26.7% received adjuvant chemotherapy. 49.2% of those were RS > 30; 93.3% of patients were RS > 25. Concordance between RS and RSPC improved when intermediate risk was defined as RS 11-25. CONCLUSIONS: This real-world data demonstrate the value of genomic tests in reducing the use of adjuvant chemotherapy in breast cancer. Incorporating clinical characteristics or RSPC scores gives additional prognostic information which may also aid clinicians' decision making.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/tratamento farmacológico , Tomada de Decisão Clínica , Recidiva Local de Neoplasia/tratamento farmacológico , Guias de Prática Clínica como Assunto/normas , Projetos de Pesquisa , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Feminino , Seguimentos , Perfilação da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Prognóstico , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Reino Unido
2.
J Hepatol ; 60(1): 110-7, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23978719

RESUMO

BACKGROUND & AIMS: Hepatocellular cancer (HCC) commonly complicates chronic liver disease and increases in incidence have been reported despite falling prevalences of viral hepatitis. METHODS: Following the introduction of centralised specialist teams to manage patients with cancer in England, we characterised the demographics of patients with HCC referred to the Newcastle-upon-Tyne Hospitals NHS Foundation Trust between 2000 and 2010. Regional HCC mortality data was from Public Health England. RESULTS: HCC related mortality in the region rose 1.8 fold in 10 years, from 2.0 to 3.7 per 100,000. 632 cases were reviewed centrally, with 2-3 fold increases in referrals of patients with associated hepatitis C, alcoholic liver disease or no chronic liver disease and a >10 fold increase in HCC associated with non-alcoholic fatty liver disease (NAFLD). By 2010 NAFLD accounted for 41/118 (34.8%) cases. Irrespective of associated etiologies, metabolic risk factors were present in 78/118 (66.1%) cases in 2010, associated with regional increases in obesity and diabetes. Median overall survival was just 10.7 months. Although patients with NAFLD associated HCC were older (71.3 yr vs. 67.1 yr; p<0.001) and their cancers less often detected by surveillance, their survival was similar to other etiologies. This was attributed to significantly higher incidental presentation (38.2%) and lower prevalence of cirrhosis (77.2%). CONCLUSIONS: HCC related mortality is increasing, with typical patients being elderly with metabolic risk factors. The prognosis for most of the cases is poor, but older patients with co-morbidities can do well, managed, within a specialist multidisciplinary team if their cancer is detected pre-symptomatically.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Neoplasias Hepáticas/mortalidade , Obesidade/complicações , Fatores Etários , Idoso , Fígado Gorduroso/complicações , Humanos , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica , Fatores de Risco
3.
BMJ Open ; 12(12): e066252, 2022 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-36585130

RESUMO

INTRODUCTION: Anthracyclines are included in chemotherapy regimens to treat several different types of cancer and are extremely effective. However, it is recognised that a significant side effect is cardiotoxicity; anthracyclines can cause irreversible damage to cardiac cells and ultimately impaired cardiac function and heart failure, which may only be evident years after exposure. The PROACT trial will establish the effectiveness of the ACE inhibitor enalapril maleate (enalapril) in preventing cardiotoxicity in patients with breast cancer and non-Hodgkin's lymphoma (NHL) receiving anthracycline-based chemotherapy. METHODS AND ANALYSIS: PROACT is a prospective, randomised, open-label, blinded end-point, superiority trial which will recruit adult patients being treated for breast cancer and NHL at NHS hospitals throughout England. The trial aims to recruit 106 participants, who will be randomised to standard care (high-dose anthracycline-based chemotherapy) plus enalapril (intervention) or standard care alone (control). Patients randomised to the intervention arm will receive enalapril (starting at 2.5 mg two times per day and titrating up to a maximum dose of 10 mg two times per day), commencing treatment at least 2 days prior to starting chemotherapy and finishing 3 weeks after their last anthracycline dose. The primary outcome is the presence or absence of cardiac troponin T release at any time during anthracycline treatment, and 1 month after the last dose of anthracycline. Secondary outcomes will focus on cardiac function measured using echocardiogram assessment, adherence to enalapril and side effects. ETHICS AND DISSEMINATION: A favourable opinion was given following research ethics committee review by West Midlands-Edgbaston REC, Ref: 17/WM/0248. Trial findings will be disseminated through engagement with patients, the oncology and cardiology communities, NHS management and commissioning groups and through peer-reviewed publication. TRIAL REGISTRATION NUMBER: NCT03265574.


Assuntos
Neoplasias da Mama , Linfoma não Hodgkin , Linfoma , Adulto , Humanos , Feminino , Neoplasias da Mama/patologia , Cardiotoxicidade/etiologia , Cardiotoxicidade/prevenção & controle , Estudos Prospectivos , Enalapril/uso terapêutico , Antibióticos Antineoplásicos/efeitos adversos , Antraciclinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
4.
Cancer Epidemiol Biomarkers Prev ; 23(1): 144-53, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24220911

RESUMO

BACKGROUND: Hepatocellular carcinoma is a common complication of chronic liver disease (CLD), and is conventionally diagnosed by radiological means. We aimed to build a statistical model that could determine the risk of hepatocellular carcinoma in individual patients with CLD using objective measures, particularly serological tumor markers. METHODS: A total of 670 patients with either CLD alone or hepatocellular carcinoma were recruited from a single UK center into a case-control study. Sera were collected prospectively and specifically for this study. A logistic regression analysis was used to determine independent factors associated with hepatocellular carcinoma and a model built and assessed in terms of sensitivity, specificity, and proportion of correct diagnoses. RESULTS: The final model involving gender, age, AFP-L3, α fetoprotein (AFP), and des-carboxy-prothrombin ("GALAD") was developed in a "discovery" data set and validated in independent data sets both from the same institution and from an external institution. When optimized for sensitivity and specificity, the model gave values of more than 0.88 irrespective of the disease stage. CONCLUSIONS: The presence of hepatocellular carcinoma can be detected in patients with CLD on the basis of a model involving objective clinical and serological factors. It is now necessary to test the model's performance in a prospective manner and in a routine clinical practice setting, to determine if it may replace or, more likely, enhance current radiological approaches. IMPACT: Our data provide evidence that an entirely objective serum biomarker-based model may facilitate the detection and diagnosis of hepatocellular carcinoma and form the basis for a prospective study comparing this approach with the standard radiological approaches.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Neoplasias Hepáticas/sangue , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes
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