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BACKGROUND: CA-125 testing is a recommended first line investigation for women presenting with possible symptoms of ovarian cancer in English primary care, to help determine whether further investigation for ovarian cancer is needed. It is currently not known how well the CA-125 test performs in ovarian cancer detection for patients from different ethnic groups. METHODS: A retrospective cohort study utilising English primary care data linked to the national cancer registry was undertaken. Women aged ≥ 40 years with a CA-125 test between 2010 and 2017 were included. Logistic regression predicted one-year ovarian cancer incidence by ethnicity, adjusting for age, deprivation status, and comorbidity score. The estimated incidence of ovarian cancer by CA-125 level was modelled for each ethnic group using restricted cubic splines. RESULTS: The diagnostic performance of CA-125 differed for women from different ethnicities. In an unadjusted analysis, predicted CA-125 levels for Asian and Black women were higher than White women at corresponding probabilities of ovarian cancer. The higher PPVs for White women compared to Asian or Black women were eliminated by inclusion of covariates. CONCLUSION: The introduction of ethnicity-specific thresholds may increase the specificity and PPVs of CA-125 in ovarian cancer detection at the expense of sensitivity, particularly for Asian and Black women. As such, we cannot recommend the use of ethnicity-specific thresholds for CA-125.
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Antígeno Ca-125 , Etnicidade , Neoplasias Ovarianas , Atenção Primária à Saúde , Humanos , Feminino , Antígeno Ca-125/sangue , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/etnologia , Neoplasias Ovarianas/epidemiologia , Pessoa de Meia-Idade , Idoso , Adulto , Estudos Retrospectivos , Estudos de Coortes , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Ovarian cancer is a challenging disease to diagnose and treat effectively with five-year survival rates below 50%. Previous patient experience research in high-income countries highlighted common challenges and opportunities to improve survival and quality of life for women affected by ovarian cancer. However, no comparable data exist for low-and middle-income countries, where 70% of women with the disease live. This study aims to address this evidence gap. METHODS: This is an observational multi-country study set in low- and middle-income countries. We aim to recruit over 2000 women diagnosed with ovarian cancer across multiple hospitals in 24 countries in Asia, Africa and South America. Country sample sizes have been calculated (n = 70-96 participants /country), taking account of varying national five-year disease prevalence rates. Women within five years of their diagnosis, who are in contact with participating hospitals, are invited to take part in the study. A questionnaire has been adapted from a tool previously used in high-income countries. It comprises 57 multiple choice and two open-ended questions designed to collect information on demographics, women's knowledge of ovarian cancer, route to diagnosis, access to treatments, surgery and genetic testing, support needs, the impact of the disease on women and their families, and their priorities for action. The questionnaire has been designed in English, translated into local languages and tested according to local ethics requirements. Questionnaires will be administered by a trained member of the clinical team. CONCLUSION: This study will inform further research, advocacy, and action in low- and middle-income countries based on tailored approaches to the national, regional and global challenges and opportunities. In addition, participating countries can choose to repeat the study to track progress and the protocol can be adapted for other countries and other diseases.
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Países em Desenvolvimento , Neoplasias Ovarianas , Qualidade de Vida , Humanos , Feminino , Neoplasias Ovarianas/terapia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/diagnóstico , Inquéritos e Questionários , Ásia/epidemiologia , África/epidemiologia , América do Sul/epidemiologia , Taxa de Sobrevida , Adulto , Pessoa de Meia-IdadeRESUMO
BACKGROUND: A history of multiple myeloma, prostate cancer, and breast cancer has been associated with adverse bone health, but associations across a broader range of cancers are unclear. We aimed to compare the risk of any bone fracture and major osteoporotic fractures in survivors of a wide range of cancers versus cancer-free individuals. METHODS: In this population-based matched cohort study, we used electronic health records from the UK Clinical Practice Research Datalink linked to hospital data. We included adults (aged ≥18 years) eligible for linkage, and we restricted the study start to Jan 2, 1998, onwards and applied administrative censoring on Jan 31, 2020. The cancer survivor group included survivors of the 20 most common cancers. Each individual with cancer was matched (age, sex, and general practice) to up to five controls (1:5) who were cancer-free. The primary outcomes were any bone fracture and any major osteoporotic fracture (pelvic, hip, wrist, spine, or proximal humeral fractures) occurring more than 1 year after index date (ie, the diagnosis date of the matched individual with cancer). We used Cox regression models, adjusted for shared risk factors, to estimate associations between cancer survivorship and bone fractures. FINDINGS: 578 160 adults with cancer diagnosed in 1998-2020 were matched to 3 226 404 cancer-free individuals. Crude incidence rates of fractures in cancer survivors ranged between 8·39 cases (95% CI 7·45-9·46) per 1000 person-years for thyroid cancer and 21·62 cases (20·18-23·18) per 1000 person-years for multiple myeloma. Compared with cancer-free individuals, the risk of any bone fracture was increased in 15 of 20 cancers, and of major osteoporotic fractures in 17 of 20 cancers. Effect sizes varied: adjusted hazard ratios (HRs) were largest for multiple myeloma (1·94, 95% CI 1·77-2·13) and prostate cancer (1·43, 1·39-1·47); HRs in the range 1·20-1·50 were seen for stomach, liver, pancreas, lung, breast, kidney, and CNS cancers; smaller associations (HR <1·20) were observed for malignant melanoma, non-Hodgkin lymphoma, leukaemia, and oesophageal, colorectal, and cervical cancers. Increased risks of major osteoporotic fracture were noted most substantially in multiple myeloma (2·25, 1·96-2·58) and CNS (2·12, 1·56-2·87), liver (1·62, 1·01-2·61), prostate (1·60, 1·53-1·67), and lung cancers (1·60, 1·44-1·77). Effect sizes tended to reduce over time since diagnosis but remained elevated for more than 5 years in several cancers, such as multiple myeloma and stomach, lung, breast, prostate, and CNS cancers. INTERPRETATION: Survivors of most types of cancer were at increased risk of bone fracture for several years after cancer, with variation by cancer type. These findings can help to inform mitigation and prevention strategies. FUNDING: Wellcome Trust.
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Neoplasias do Sistema Nervoso Central , Mieloma Múltiplo , Fraturas por Osteoporose , Neoplasias da Próstata , Masculino , Feminino , Humanos , Adolescente , Adulto , Estudos de Coortes , Registros Eletrônicos de Saúde , SobreviventesRESUMO
BACKGROUND: Understanding pre-diagnostic prescribing activity could reveal windows during which more timely cancer investigation and detection may occur. AIM: To examine prescription patterns for common urological clinical features prior to renal and bladder cancer diagnoses. DESIGN AND SETTING: A retrospective cohort study was performed using electronic primary care and cancer registry data on patients with bladder and renal cancer, who received their diagnosis between April 2012 and December 2015 in England. METHOD: Primary care prescriptions up to 2 years pre- diagnosis were analysed for five groups of clinical features (irritative urological symptoms, obstructive symptoms, urinary tract infections [UTIs], genital infections, and atrophic vaginitis). Poisson regressions estimating the inflection point from which the rate of prescriptions increased from baseline were used to identify the start of diagnostic windows during which cancer could be detected. RESULTS: A total of 48 094 prescriptions for 5322 patients were analysed. Inflection points for an increase in UTI prescriptions were identified 9 months pre- diagnosis for renal (95% confidence interval [CI] = 5.3 to 12.7) and bladder (95% CI = 7.4 to 10.6) cancers. For bladder cancer, the change in UTI antibiotic prescription rates occurred 4 months earlier in females (11 months pre- diagnosis, 95% CI = 9.7 to 12.3) than in males (7 months pre-diagnosis, 95% CI = 5.4 to 8.6). For other clinical features, no inflection points were identified and, as such, no diagnostic windows could be defined. CONCLUSION: Prescription rates for UTIs increased 9 months before bladder and renal cancer diagnoses, indicating that there is potential to expedite diagnosis of these cancers in patients presenting with features of UTI. The greatest opportunity for more timely diagnosis may be in females with bladder cancer, who experienced the earliest increase in UTI prescription rate.
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Neoplasias Renais , Padrões de Prática Médica , Neoplasias da Bexiga Urinária , Infecções Urinárias , Humanos , Neoplasias da Bexiga Urinária/diagnóstico , Feminino , Masculino , Estudos Retrospectivos , Neoplasias Renais/diagnóstico , Padrões de Prática Médica/estatística & dados numéricos , Infecções Urinárias/diagnóstico , Infecções Urinárias/tratamento farmacológico , Idoso , Inglaterra/epidemiologia , Pessoa de Meia-Idade , Estudos Longitudinais , Atenção Primária à Saúde , Prescrições de Medicamentos/estatística & dados numéricos , Antibacterianos/uso terapêutico , Detecção Precoce de Câncer , Sistema de Registros , AdultoRESUMO
BACKGROUND: The majority of colorectal cancer is diagnosed in patients following symptomatic presentation in the UK. AIM: To identify windows of opportunity for timely investigations or referrals in patients presenting with colon and rectal cancer-relevant symptoms or abnormal blood tests. DESIGN AND SETTING: A retrospective cohort study was undertaken using linked primary care and cancer registry data for patients with colorectal cancer diagnosed in England between 2012 and 2015. METHOD: Monthly consultation rates for relevant clinical features (change in bowel habit, rectal bleeding, abdominal pain, abdominal mass, constitutional symptoms, and other bowel symptoms) and abnormal blood test results (low haemoglobin, high platelets, and high inflammatory markers) up to 24 months pre-diagnosis were calculated. Poisson regression adjusted for age, sex, and relevant comorbidities was used to estimate the most likely month when consultation rates increased above baseline. RESULTS: In total, 5033 patients with colon cancer and 2516 with rectal cancer were included. Consultations for all examined clinical features and abnormal blood tests increased in the year pre-diagnosis. Rectal bleeding was the earliest clinical feature to increase from the baseline rate: at 10 months (95% confidence interval [CI] = 8.3 to 11.7) pre-diagnosis for colon cancer and at 8 months (95% CI = 6.1 to 9.9) pre-diagnosis for rectal cancer. Low haemoglobin, high platelets, and high inflammatory markers increased from as early as 9 months pre-diagnosis. CONCLUSION: This study found evidence for an early increase in rates of consultation for relevant clinical features and abnormal blood tests in patients with colorectal cancer, suggesting that earlier instigation of cancer-specific investigations or referrals may be warranted in some patients who were symptomatic.
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Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Neoplasias Colorretais/diagnóstico , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Testes Hematológicos , Hemoglobinas , Humanos , Estudos RetrospectivosRESUMO
Human epididymis 4 (HE4) is a promising ovarian cancer biomarker, but it has not been evaluated in primary care. In this prospective observational study, we investigated the diagnostic accuracy of HE4 alone and in combination with CA125 for the detection of ovarian cancer in symptomatic women attending primary care. General practitioner (GP)-requested CA125 samples were tested for HE4 at a large teaching hospital in Manchester, and cancer outcomes were tracked for 12 months. We found a low incidence of ovarian cancer in primary care; thus, the cohort was enriched with pre-surgical samples from 81 ovarian cancer patients. The Risk of Ovarian Malignancy Algorithm (ROMA) was calculated using age (>51) as a surrogate for menopause. Conventional diagnostic accuracy metrics were determined. A total of 1229 patients were included; 82 had ovarian cancer. Overall, ROMA performed best (AUC-0.96 (95%CI: 0.94−0.98, p = <0.001)). In women under 50 years, the combination of CA125 and HE4 (either marker positive) was superior (sensitivity: 100% (95%CI: 81.5−100.0), specificity: 80.1% (95%CI 76.7−83.1)). In women over 50, ROMA performed best (sensitivity: 84.4% (95%CI: 73.1−92.2), specificity: 87.2% (95%CI 84.1−90)). HE4 and ROMA may improve ovarian cancer detection in primary care, particularly for women under 50 years, in whom diagnosis is challenging. Validation in a larger primary care cohort is required.
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CA125 is widely used as an initial investigation in women presenting with symptoms of possible ovarian cancer. We sought to develop CA125-based diagnostic prediction models and to explore potential implications of implementing model-based thresholds for further investigation in primary care. This retrospective cohort study used routinely collected primary care and cancer registry data from symptomatic, CA125-tested women in England (2011-2014). A total of 29,962 women were included, of whom 279 were diagnosed with ovarian cancer. Logistic regression was used to develop two models to estimate ovarian cancer probability: Model 1 consisted of age and CA125 level; Model 2 incorporated further risk factors. Model discrimination (AUC) was evaluated using 10-fold cross-validation. The sensitivity and specificity of various model risk thresholds (≥1% to ≥3%) were compared with that of the current CA125 cut-off (≥35 U/mL). Model 1 exhibited excellent discrimination (AUC: 0.94) on cross-validation. The inclusion of additional variables (Model 2) did not improve performance. At a risk threshold of ≥1%, Model 1 exhibited greater sensitivity (86.4% vs. 78.5%) but lower specificity (89.1% vs. 94.5%) than CA125 (≥35 U/mL). Applying the ≥1% model threshold to the cohort in place of the current CA125 cut-off, 1 in every 74 additional women identified had ovarian cancer. Following external validation, Model 1 could be used as part of a 'risk-based triage' system in which women at high risk of undiagnosed ovarian cancer are selected for urgent specialist investigation, while women at 'low risk but not no risk' are offered non-urgent investigation or interval CA125 re-testing. Such an approach has the potential to expedite ovarian cancer diagnosis, but further research is needed to evaluate the clinical impact and health-economic implications.
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INTRODUCTION: The use of Human Epididymis Protein 4 (HE4) as a biomarker for ovarian cancer is gaining traction, providing the impetus for development of a high throughput automated HE4 assay that is comparable to the conventional manual enzyme immunometric-assay (EIA). The aim of this study was to compare two immunoassay methods for the measurement of serum HE4. MATERIALS AND METHODS: 1348 serum samples were analysed for serum HE4 using both the EIA and the automated chemiluminescent immunoassay (CLEIA) methods. HE4 values were compared using a Passing-Bablok regression and agreement assessed using Lin's concordance correlation coefficient (CCC). The absolute and percentage bias of the CLEIA compared to EIA was determined. RESULTS: There was moderate agreement between the two methods (CCC 0.929, 95%CI 0.923-0.936). Passing-Bablok regression demonstrated an overestimation of the CLEIA [constant 4.44 (95%CI 2.96-5.68), slope 1.04 (95%CI 1.02-1.07)]. The CLEIA method had a mean percentage bias of 16.25% compared to the EIA method. CONCLUSION: The CLEIA significantly overestimated serum HE4 values compared to the EIA, which could impact clinical interpretation and patient management. Further studies are required to develop an appropriate cut-off depending on the population being investigated and the analytic method being used.
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BACKGROUND: In the UK, the cancer antigen 125 (CA125) test is recommended as a first-line investigation in women with symptoms of possible ovarian cancer. AIM: To compare time between initial primary care CA125 test and diagnosis, tumour morphology, and stage in women with normal (<35 U/ml) and abnormal (≥35 U/ml) CA125 levels prior to ovarian cancer diagnosis. DESIGN AND SETTING: Retrospective cohort study using English primary care and cancer registry data. METHOD: Associations between CA125 test results and test-to-diagnosis interval, stage, and ovarian cancer morphology were examined. RESULTS: In total, 456 women were diagnosed with ovarian cancer in the 12 months after having a CA125 test. Of these, 351 (77%) had an abnormal, and 105 (23%) had a normal, CA125 test result. The median test-to-diagnosis interval was 35 days (interquartile range [IQR] 21-53) for those with abnormal CA125 levels, and 64 days (IQR 42-127) for normal CA125 levels. Tumour morphology differed by CA125 result: indolent borderline tumours were less common in those with abnormal CA125 levels (n = 47, 13%) than those with normal CA125 levels (n = 51, 49%) (P<0.001). Staging data were available for 304 women with abnormal, and 77 with normal, CA125 levels. Of those with abnormal CA125 levels, 35% (n = 106) were diagnosed at an early stage, compared to 86% (n = 66) of women with normal levels. The odds of being diagnosed with early-stage disease were higher in women with normal as opposed to abnormal CA125 levels (odds ratio 12.2, 95% confidence interval = 5.8 to 25.1, P<0.001). CONCLUSION: Despite longer intervals between testing and diagnosis, women with normal, compared with abnormal, CA125 levels more frequently had indolent tumours and were more commonly diagnosed at an early stage in the course of the disease. Although testing approaches that have greater sensitivity might expedite diagnosis for some women, it is not known if this would translate to earlier-stage diagnosis.
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Antígeno Ca-125 , Neoplasias Ovarianas , Registros Eletrônicos de Saúde , Feminino , Humanos , Neoplasias Ovarianas/diagnóstico , Atenção Primária à Saúde , Estudos RetrospectivosRESUMO
INTRODUCTION: Lower gastrointestinal (GI) cancers are a major cause of cancer deaths worldwide. Prognosis improves with earlier diagnosis, and non-invasive biomarkers have the potential to aid with early detection. Substantial investment has been made into the development of biomarkers; however, studies are often carried out in specialist settings and few have been evaluated for low-prevalence populations. METHODS: We aimed to identify novel biomarkers for the detection of lower GI cancers that have the potential to be evaluated for use in primary care. MEDLINE, Embase, Emcare and Web of Science were systematically searched for studies published in English from January 2000 to October 2019. Reference lists of included studies were also assessed. Studies had to report on measures of diagnostic performance for biomarkers (single or in panels) used to detect colorectal or anal cancers. We included all designs and excluded studies with fewer than 50 cases/controls. Data were extracted from published studies on types of biomarkers, populations and outcomes. Narrative synthesis was used, and measures of specificity and sensitivity were meta-analysed where possible. RESULTS: We identified 142 studies reporting on biomarkers for lower GI cancers, for 24,844 cases and 45,374 controls. A total of 378 unique biomarkers were identified. Heterogeneity of study design, population type and sample source precluded meta-analysis for all markers except methylated septin 9 (mSEPT9) and pyruvate kinase type tumour M2 (TuM2-PK). The estimated sensitivity and specificity of mSEPT9 was 80.6% (95% CI 76.6-84.0%) and 88.0% (95% CI 79.1-93.4%) respectively; TuM2-PK had an estimated sensitivity of 81.6% (95% CI 75.2-86.6%) and specificity of 80.1% (95% CI 76.7-83.0%). CONCLUSION: Two novel biomarkers (mSEPT9 and TuM2-PK) were identified from the literature with potential for use in lower-prevalence populations. Further research is needed to validate these biomarkers in primary care for screening and assessment of symptomatic patients.
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Detecção Precoce de Câncer , Neoplasias Gastrointestinais , Biomarcadores , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/epidemiologia , Humanos , Prevalência , Sensibilidade e EspecificidadeRESUMO
Colorectal cancer (CRC) is the third most common cancer worldwide. Primary care professionals can play an important role in both prevention and early detection of CRC. Most CRCs are attributed to modifiable lifestyle factors, which can be addressed within primary care, and promotion of population-based screening programmes can aid early cancer detection in asymptomatic patients. Primary care professionals have a vital role in clinically assessing patients presenting with symptoms that may indicate cancer, as most patients with CRC first present with symptoms. These assessments are often challenging-many of the symptoms of CRC are non-specific and commonly occur in patients presenting with non-malignant disease. The range of options for investigating symptomatic patients in primary care is rapidly growing. Simple tests, such as faecal immunochemical testing (FIT), are now being used to guide decisions around referral for more invasive tests, such as colonoscopy, while direct access to specialist investigations is also becoming more common. Clinical decision support tools (CDSTs) which calculate cancer risk based on symptomatology, patient characteristics and test results can provide an additional resource to guide decisions on further investigation. This article explores the challenges of CRC prevention and detection from the primary care perspective, discusses current evidence-based approaches for CRC detection used in primary care (with examples from UK guidelines), and highlights emerging research which may likely alter practice in the future.
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Neoplasias Colorretais , Sangue Oculto , Colonoscopia , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer , Humanos , Atenção Primária à SaúdeRESUMO
BACKGROUND: National guidelines in England recommend prompt chest X-ray (within 14 days) in patients presenting in general practice with unexplained symptoms of possible lung cancer, including persistent cough, shortness of breath, or weight loss. AIM: To examine time to chest X-ray in symptomatic patients in English general practice before lung cancer diagnosis, and explore demographical variation. DESIGN AND SETTING: Retrospective cohort study using routinely collected general practice, cancer registry, and imaging data from England. METHOD: Patients with lung cancer who presented symptomatically in general practice in the year pre-diagnosis and who had a pre-diagnostic chest X-ray were included. Time from presentation to chest X-ray (presentation-test interval) was determined and intervals classified based on national guideline recommendations as concordant (≤14 days) or non-concordant (>14 days). Variation in intervals was examined by age, sex, smoking status, and deprivation. RESULTS: In a cohort of 2102 patients with lung cancer, the median presentation-test interval was 49 (interquartile range [IQR] 5-172) days. Of these, 727 (35%) patients had presentation-test intervals of ≤14 days (median 1 [IQR 0-6] day) and 1375 (65%) had presentation-test intervals of >14 days (median 128 [IQR 52-231] days). Intervals were longer among patients who smoke (equivalent to 63% longer than non-smokers; P<0.001), older patients (equivalent to 7% longer for every 10 years from age 27; P = 0.013), and females (equivalent to 12% longer than males; P = 0.016). CONCLUSION: In symptomatic primary care patients who underwent chest X-ray before lung cancer diagnosis, only 35% were tested within the timeframe recommended by national guidelines. Patients who smoke, older patients, and females experienced longer intervals. These findings could help guide initiatives aimed at improving timely lung cancer diagnosis.
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Registros Eletrônicos de Saúde , Neoplasias Pulmonares , Adulto , Estudos de Coortes , Inglaterra , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Atenção Primária à Saúde , Estudos Retrospectivos , Raios XRESUMO
BACKGROUND: Breast cancer is the most common cancer diagnosed in women globally, and 5-year net survival probabilities in high-income countries are generally >80%. A cancer diagnosis and treatment are often traumatic events, and many women struggle to cope during this period. Less is known, however, about the long-term mental health impact of the disease, despite many women living several years beyond their breast cancer and mental health being a major source of disability in modern societies. The objective of this study was to quantify the risk of several adverse mental health-related outcomes in women with a history of breast cancer followed in primary care in the United Kingdom National Health Service, compared to similar women who never had cancer. METHODS AND FINDINGS: We conducted a matched cohort study using data routinely collected in primary care across the UK to quantify associations between breast cancer history and depression, anxiety, and other mental health-related outcomes. All women with incident breast cancer in the Clinical Practice Research Datalink (CPRD) GOLD primary care database between 1988 and 2018 (N = 57,571, mean = 62 ± 14 years) were matched 1:4 to women with no prior cancer (N = 230,067) based on age, primary care practice, and eligibility of the data for linkage to hospital data sources. Cox models were used to estimate associations between breast cancer survivorship and each mental health-related outcome, further adjusting for diabetes, body mass index (BMI), and smoking and drinking status at baseline. Breast cancer survivorship was positively associated with anxiety (adjusted hazard ratio (HR) = 1.33; 95% confidence interval (CI): 1.29-1.36; p < 0.001), depression (1.35; 1.32-1.38; p < 0.001), sexual dysfunction (1.27; 1.17-1.38; p < 0.001), and sleep disorder (1.68; 1.63-1.73; p < 0.001), but not with cognitive dysfunction (1.00; 0.97-1.04; p = 0.88). Positive associations were also found for fatigue (HR = 1.28; 1.25-1.31; p < 0.001), pain (1.22; 1.20-1.24; p < 0.001), receipt of opioid analgesics (1.86; 1.83-1.90; p < 0.001), and fatal and nonfatal self-harm (1.15; 0.97-1.36; p = 0.11), but CI was wide, and the relationship was not statistically significant for the latter. HRs for anxiety and depression decreased over time (p-interaction <0.001), but increased risks persisted for 2 and 4 years, respectively, after cancer diagnosis. Increased levels of pain and sleep disorder persisted for 10 years. Younger age was associated with larger HRs for depression, cognitive dysfunction, pain, opioid analgesics use, and sleep disorders (p-interaction <0.001 in each case). Limitations of the study include the potential for residual confounding by lifestyle factors and detection bias due to cancer survivors having greater healthcare contact. CONCLUSIONS: In this study, we observed that compared to women with no prior cancer, breast cancer survivors had higher risk of anxiety, depression, sleep problems, sexual dysfunction, fatigue, receipt of opioid analgesics, and pain. Relative risks estimates tended to decrease over time, but anxiety and depression were significantly increased for 2 and 4 years after breast cancer diagnosis, respectively, while associations for fatigue, pain, and sleep disorders were elevated for at least 5-10 years after diagnosis. Early diagnosis and increased awareness among patients, healthcare professionals, and policy makers are likely to be important to mitigate the impacts of these raised risks.
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Neoplasias da Mama/psicologia , Transtornos Mentais/psicologia , Sobrevivência , Neoplasias da Mama/epidemiologia , Feminino , Humanos , Incidência , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Risco , Reino Unido/epidemiologiaRESUMO
INTRODUCTION: Detecting upper gastrointestinal (GI) cancers in primary care is challenging, as cancer symptoms are common, often non-specific, and most patients presenting with these symptoms will not have cancer. Substantial investment has been made to develop biomarkers for cancer detection, but few have reached routine clinical practice. We aimed to identify novel biomarkers for upper GI cancers which have been sufficiently validated to be ready for evaluation in low-prevalence populations. METHODS: We systematically searched MEDLINE, Embase, Emcare, and Web of Science for studies published in English from January 2000 to October 2019 (PROSPERO registration CRD42020165005). Reference lists of included studies were assessed. Studies had to report on second measures of diagnostic performance (beyond discovery phase) for biomarkers (single or in panels) used to detect pancreatic, oesophageal, gastric, and biliary tract cancers. We included all designs and excluded studies with less than 50 cases/controls. Data were extracted on types of biomarkers, populations and outcomes. Heterogeneity prevented pooling of outcomes. RESULTS: We identified 149 eligible studies, involving 22,264 cancer cases and 49,474 controls. A total of 431 biomarkers were identified (183 microRNAs and other RNAs, 79 autoantibodies and other immunological markers, 119 other proteins, 36 metabolic markers, 6 circulating tumour DNA and 8 other). Over half (n = 231) were reported in pancreatic cancer studies. Only 35 biomarkers had been investigated in at least two studies, with reported outcomes for that individual marker for the same tumour type. Apolipoproteins (apoAII-AT and apoAII-ATQ), and pepsinogens (PGI and PGII) were the most promising biomarkers for pancreatic and gastric cancer, respectively. CONCLUSION: Most novel biomarkers for the early detection of upper GI cancers are still at an early stage of matureness. Further evidence is needed on biomarker performance in low-prevalence populations, in addition to implementation and health economic studies, before extensive adoption into clinical practice can be recommended.
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Neoplasias Gastrointestinais , Neoplasias Pancreáticas , Biomarcadores , Detecção Precoce de Câncer , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/epidemiologia , Humanos , PrevalênciaRESUMO
In the absence of effective ovarian cancer screening programs, most women are diagnosed following the onset of symptoms. Symptom-based tools, including symptom checklists and risk prediction models, have been developed to aid detection. The aim of this systematic review was to identify and compare the diagnostic performance of these tools. We searched MEDLINE, EMBASE and Cochrane CENTRAL, without language restriction, for relevant studies published between 1 January 2000 and 3 March 2020. We identified 1625 unique records and included 16 studies, evaluating 21 distinct tools in a range of settings. Fourteen tools included only symptoms; seven also included risk factors or blood tests. Four tools were externally validated-the Goff Symptom Index (sensitivity: 56.9-83.3%; specificity: 48.3-98.9%), a modified Goff Symptom Index (sensitivity: 71.6%; specificity: 88.5%), the Society of Gynaecologic Oncologists consensus criteria (sensitivity: 65.3-71.5%; specificity: 82.9-93.9%) and the QCancer Ovarian model (10% risk threshold-sensitivity: 64.1%; specificity: 90.1%). Study heterogeneity precluded meta-analysis. Given the moderate accuracy of several tools on external validation, they could be of use in helping to select women for ovarian cancer investigations. However, further research is needed to assess the impact of these tools on the timely detection of ovarian cancer and on patient survival.