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1.
Lung Cancer ; 173: 1-4, 2022 11.
Article in English | MEDLINE | ID: mdl-36099795

ABSTRACT

Here we report the prevalence of incidental findings (IF) in the Manchester Lung Health Check pilot, which delivered mobile low-dose CT targeted lung cancer screening. 187 IFs were reported in 158 participants (11.2 % of individuals screened; n = 1,409). 101 IFs in 90 participants (6.4 %) were concerning for extra-pulmonary malignancy. IFs resulted in 118 imaging studies, 20 invasive investigations, and 106 new diagnoses, including 5 malignancies (0.35 %). Clinical management of IFs required 84 specialist reviews (6.0 %), 34 medication changes (2.4 %) and 10 interventional treatments (0.71 %). Lung cancer screening detects clinically relevant IFs but further research is needed to better understand the potential benefits and harms of such findings to participants.


Subject(s)
Early Detection of Cancer , Lung Neoplasms , Humans , Early Detection of Cancer/methods , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/epidemiology , Incidental Findings , Smokers , Tomography, X-Ray Computed/methods , Lung , Mass Screening/methods
2.
Health Syst (Basingstoke) ; 10(4): 337-347, 2021.
Article in English | MEDLINE | ID: mdl-34745593

ABSTRACT

Without timely assessments of the number of COVID-19 cases requiring hospitalisation, healthcare providers will struggle to ensure an appropriate number of beds are made available. Too few could cause excess deaths while too many could result in additional waits for elective treatment. As well as supporting capacity considerations, reliably projecting future "waves" is important to inform the nature, timing and magnitude of any localised restrictions to reduce transmission. In making the case for locally owned and locally configurable models, this paper details the approach taken by one major healthcare system in founding a multi-disciplinary "Scenario Review Working Group", comprising commissioners, public health officials and academic epidemiologists. The role of this group, which met weekly during the pandemic, was to define and maintain an evolving library of plausible scenarios to underpin projections obtained through an SEIR-based compartmental model. Outputs have informed decision-making at the system's major incident Bronze, Silver and Gold Commands. This paper presents illustrated examples of use and offers practical considerations for other healthcare systems that may benefit from such a framework.

3.
Lung Cancer ; 124: 148-153, 2018 10.
Article in English | MEDLINE | ID: mdl-30268454

ABSTRACT

BACKGROUND: Cardiovascular disease (CVD) is a major cause of morbidity and mortality in populations eligible for lung cancer screening. The aim of this study was to determine whether a brief CV risk assessment, delivered as part of a targeted community-based lung cancer screening programme, was effective in identifying individuals at high risk who might benefit from primary prevention. METHODS: The Manchester Lung Screening Pilot consisted of annual low dose CT (LDCT) over 2 screening rounds, targeted at individuals in deprived areas at high risk of lung cancer (age 55-74 and 6-year risk ≥1.51%, using PLCOM2012 risk model). All participants of the second screening round were eligible to take part in the study. Ten-year CV risk was estimated using QRISK2 in participants without CVD and compared to age (±5 years) and sex matched Health Survey for England (HSE) controls; high risk was defined as QRISK2 score ≥10%. Coronary artery calcification (CAC) was assessed on LDCT scans and compared to QRISK2 score. RESULTS: Seventy-seven percent (n=920/1,194) of screening attendees were included in the analysis; mean age 65.6 ± 5.4 and 50.4% female. QRISK2 and lung cancer risk (PLCOM2012) scores were correlated (r = 0.26, p < 0.001). Median QRISK2 score was 21.1% (IQR 14.9-29.6) in those without established CVD (77.6%, n = 714/920), double that of HSE controls (10.3%, IQR 6.6-16.2; n = 714) (p < 0.001). QRISK2 score was significantly higher in those with CAC (p < 0.001). Screening attendees were 10-fold more likely to be classified high risk (OR 10.2 [95% CI 7.3-14.0]). One third (33.7%, n = 310/920) of all study participants were high risk but not receiving statin therapy for primary CVD prevention. DISCUSSION: Opportunistic CVD risk assessment within a targeted lung cancer screening programme is feasible and is likely to identify a very large number of individuals suitable for primary prevention.


Subject(s)
Cardiovascular Diseases/diagnosis , Early Detection of Cancer/methods , Lung Neoplasms/diagnosis , Aged , Calcinosis , Cardiovascular Diseases/epidemiology , England/epidemiology , Female , Humans , Lung Neoplasms/epidemiology , Male , Middle Aged , Risk , Risk Assessment
4.
BMJ Open ; 6(1): e010589, 2016 Jan 27.
Article in English | MEDLINE | ID: mdl-26817643

ABSTRACT

INTRODUCTION: Histological diagnosis of malignant mesothelioma requires an invasive procedure such as CT-guided needle biopsy, thoracoscopy, video-assisted thorascopic surgery (VATs) or thoracotomy. These invasive procedures encourage tumour cell seeding at the intervention site and patients can develop tumour nodules within the chest wall. In an effort to prevent nodules developing, it has been widespread practice across Europe to irradiate intervention sites postprocedure--a practice known as prophylactic irradiation of tracts (PIT). To date there has not been a suitably powered randomised trial to determine whether PIT is effective at reducing the risk of chest wall nodule development. METHODS AND ANALYSIS: In this multicentre phase III randomised controlled superiority trial, 374 patients who can receive radiotherapy within 42 days of a chest wall intervention will be randomised to receive PIT or no PIT. Patients will be randomised on a 1:1 basis. Radiotherapy in the PIT arm will be 21 Gy in three fractions. Subsequent chemotherapy is given at the clinicians' discretion. A reduction in the incidence of chest wall nodules from 15% to 5% in favour of radiotherapy 6 months after randomisation would be clinically significant. All patients will be followed up for up to 2 years with monthly telephone contact and at least four outpatient visits in the first year. ETHICS AND DISSEMINATION: PIT was approved by NRES Committee North West-Greater Manchester West (REC reference 12/NW/0249) and recruitment is currently on-going, the last patient is expected to be randomised by the end of 2015. The analysis of the primary end point, incidence of chest wall nodules 6 months after randomisation, is expected to be published in 2016 in a peer reviewed journal and results will also be presented at scientific meetings and summary results published online. A follow-up analysis is expected to be published in 2018. TRIAL REGISTRATION NUMBER: ISRCTN04240319; NCT01604005; Pre-results.


Subject(s)
Lung Neoplasms/prevention & control , Mesothelioma/prevention & control , Neoplasm Seeding , Pleural Neoplasms/prevention & control , Postoperative Complications/prevention & control , Adult , Aged , Ambulatory Care , Antineoplastic Agents/therapeutic use , Chemotherapy, Adjuvant , Clinical Protocols , Female , Humans , Lung Neoplasms/radiotherapy , Lung Neoplasms/surgery , Male , Mesothelioma/radiotherapy , Mesothelioma/surgery , Mesothelioma, Malignant , Patient Selection , Pleural Neoplasms/radiotherapy , Pleural Neoplasms/surgery , Postoperative Care/methods , Radiotherapy, Adjuvant , Thoracic Neoplasms/prevention & control , Thoracic Neoplasms/secondary , Thoracic Wall , Treatment Outcome , Young Adult
6.
Thorax ; 68(8): 786-7, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23842821

ABSTRACT

Flexible bronchoscopy is an essential, established and expanding tool in respiratory medicine. Its practice, however, needs to be safe, effective and for the right indications to maximise clinical utility. This guideline is based on the best available evidence and is a revised update of the British Thoracic Society guideline on diagnostic flexible bronchoscopy.


Subject(s)
Bronchoscopy/standards , Practice Guidelines as Topic , Societies, Medical , Thoracic Diseases/diagnosis , Adult , Humans , United Kingdom
7.
Ann Oncol ; 21(10): 2023-2028, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20332134

ABSTRACT

BACKGROUND: Some non-small-cell lung cancer (NSCLC) surgical series have indicated that the positive prognostic effect of female sex is limited to patients with adenocarcinoma. We carried out a retrospective analysis to investigate the role of sex and histology on efficacy, toxicity, and dose delivery after chemotherapy. PATIENT AND METHODS: Individual patient data were pooled from five randomized, phase III, advanced NSCLC chemotherapy trials. Primary outcomes were response rate, overall survival (OS), toxicity, and dose delivery. A secondary analysis examined survival by sex in histological subgroups. RESULTS: Of 2349 patients, 34% were women. Women had a higher response rate to chemotherapy (42% versus 40%, P = 0.01) and longer survival than men (median OS 9.6 versus 8.6 months, P = 0.002). The difference in OS remained after adjusting for age, stage, performance status, and histology (hazard ratio 0.83, 95% confidence interval 0.74-0.92, P = 0.0005). Upon further examination, longer survival in women was only seen in patients with adenocarcinoma (test for interaction P = 0.006). There were no differences in hematological toxicity or transfusions. Women experienced more grade 3-4 emesis than men (P < 0.0001) and more dose delays (P = 0.02) or dose reductions (P < 0.0001). CONCLUSION: The positive prognostic effect among women is confirmed in patients receiving platinum-based chemotherapy but appears confined to those with adenocarcinoma histology.


Subject(s)
Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/mortality , Female , Follow-Up Studies , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/mortality , Male , Middle Aged , Quality of Life , Randomized Controlled Trials as Topic , Retrospective Studies , Sex Factors , Survival Rate , Treatment Outcome , Young Adult
8.
Ann Oncol ; 17(7): 1111-9, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16603599

ABSTRACT

BACKGROUND: Phase III studies suggest that non-small-cell lung cancer (NSCLC) patients treated with cisplatin-docetaxel may have higher response rates and better survival compared with other platinum-based regimens. We report the final results of a randomised phase III study of docetaxel and carboplatin versus MIC or MVP in patients with advanced NSCLC. PATIENTS AND METHODS: Patients with biopsy proven stage III-IV NSCLC not suitable for curative surgery or radiotherapy were randomised to receive four cycles of either DCb (docetaxel 75 mg/m(2), carboplatin AUC 6), or MIC/MVP (mitomycin 6 mg/m(2), ifosfamide 3 g/m(2) and cisplatin 50 mg/m(2) or mitomycin 6 mg/m(2), vinblastine 6 mg/m(2) and cisplatin 50 mg/m(2), respectively), 3 weekly. The primary end point was survival, secondary end points included response rates, toxicity and quality of life. RESULTS: The median follow-up was 17.4 months. Overall response rate was 32% for both arms (partial response = 31%, complete response = 1%); 32% of MIC/MVP and 26% of DCb patients had stable disease. One-year survival was 39% and 35% for DCb and MIC/MVP, respectively. Two-year survival was 13% with both arms. Grade 3/4 neutropenia (74% versus 43%, P < 0.005), infection (18% versus 9%, P = 0.01) and mucositis (5% versus 1%, P = 0.02) were more common with DCb than MIC/MVP. The MIC/MVP arm had significant worsening in overall EORTC score and global health status whereas the DCb arm showed no significant change. CONCLUSIONS: The combination of DCb had similar efficacy to MIC/MVP but quality of life was better maintained.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Quality of Life , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/administration & dosage , Carboplatin/adverse effects , Carcinoma, Non-Small-Cell Lung/mortality , Cisplatin/administration & dosage , Cisplatin/adverse effects , Docetaxel , Female , Humans , Ifosfamide/administration & dosage , Ifosfamide/adverse effects , Lung Neoplasms/mortality , Male , Middle Aged , Mitomycin/administration & dosage , Mitomycin/adverse effects , Neoplasm Staging , Survival Analysis , Taxoids/administration & dosage , Taxoids/adverse effects , Vinblastine/administration & dosage , Vinblastine/adverse effects
9.
Br J Cancer ; 93(6): 719-29, 2005 Sep 19.
Article in English | MEDLINE | ID: mdl-16222316

ABSTRACT

Aurora kinases are key regulators of chromosome segregation during mitosis. We have previously shown by microarray analysis of primary lung carcinomas and matched normal tissue that AURKB (22 out of 37) and AURKA (15 out of 37) transcripts are frequently over-represented in these tumours. We now confirm these observations in a second series of 44 carcinomas and also show that aurora B kinase protein levels are raised in the tumours compared to normal tissue. Elevated levels of expression in tumours are not a consequence of high-level amplification of the AURKB gene. Using a coding sequence polymorphism we show that in most cases (seven out of nine) tumour expression is predominantly driven from one AURKB allele. Given the function of aurora B kinase, we examined whether there was an association between expression levels and genetic instability. We defined two groups of high and low AURKB expression. Using a panel of 10 microsatellite markers, we found that the group showing the higher level of expression had a higher frequency of allelic imbalance (P=0.0012). Analysis of a number of other genes that are strongly and specifically expressed in tumour over normal lung, including SERPINB5, TERT and PRAME, showed marked allelic expression imbalances in the tumour tissue in the context of balanced or only marginally imbalanced relative allelic copy numbers. Our data support a model of early carcinogenesis wherein defects in the process of inactivation of lung stem-cell associated genes during differentiation, contributes to the development of carcinogenesis.


Subject(s)
Allelic Imbalance , Carcinoma, Non-Small-Cell Lung/enzymology , Gene Expression Regulation, Enzymologic , Lung Neoplasms/enzymology , Protein Serine-Threonine Kinases/genetics , Antigens, Neoplasm/genetics , Antigens, Neoplasm/metabolism , Aurora Kinase A , Aurora Kinase B , Aurora Kinases , Biomarkers, Tumor/metabolism , Blotting, Western , Carcinoma, Non-Small-Cell Lung/pathology , Catalytic Domain , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Epithelial Cells/metabolism , Epithelial Cells/pathology , Genes, Tumor Suppressor , Humans , Lung Neoplasms/pathology , Microsatellite Repeats , Polymorphism, Restriction Fragment Length , Protein Serine-Threonine Kinases/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Serine Proteinase Inhibitors/genetics , Serine Proteinase Inhibitors/metabolism , Serpins/genetics , Serpins/metabolism , Telomerase/genetics , Telomerase/metabolism , Up-Regulation
11.
Am J Kidney Dis ; 34(5): 937-41, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10561153

ABSTRACT

During recent years it has been shown conclusively that the incidence of malignancy in systemic sclerosis (SSc) is significantly increased and that rapidly progressive skin thickening, among other factors, is a strong predictor of scleroderma renal crisis (SRC). We present a case of carcinoma of the breast presenting concurrently with SSc that subsequently progressed to dialysis-dependent renal failure in just 1 month. We discuss the possible relationship between SSc and malignancy at a cellular level. In conclusion, we recommend that patients with rapidly progressive SSc and SRC at an early stage be screened for malignancy. In those patients developing malignancy in SSc, a careful vigil for accelerated renal, cardiac, and pulmonary complications should also be undertaken.


Subject(s)
Breast Neoplasms/diagnosis , Carcinoma, Ductal, Breast/diagnosis , Paraneoplastic Syndromes/diagnosis , Renal Insufficiency/diagnosis , Scleroderma, Systemic/diagnosis , Biopsy , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Female , Humans , Kidney Glomerulus/pathology , Middle Aged , Paraneoplastic Syndromes/pathology , Renal Artery/pathology , Renal Insufficiency/pathology , Scleroderma, Systemic/pathology
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