S G Spiro

Royal Brompton and Harefield NHS Foundation Trust, Harefield, England, United Kingdom

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Publications (179)1264.54 Total impact

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    Stephen G Spiro · Allan Hackshaw
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    ABSTRACT: Low-dose CT screening for lung cancer is effective but expensive. Therefore, cheaper or more focused screening strategies may be required. LungSEARCH is a randomised prospective trial of 1568 high-risk individuals (ie, current or former moderate to heavy smokers with mild/moderate COPD) who undergo either annual sputum cytology/cytometry testing or no screening. Those with abnormal sputum then receive annual CT and fluorescent bronchoscopy for the remainder of 5 years, to identify early stage lung cancer. It is hoped that these simple initial tests could identify those requiring expensive CT scans, and the aim is to demonstrate a stage shift towards early stage cancers.Trial registration numbers ISRCTN: ISRCTN80745975, clinicaltrials.gov: NCT00512746. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Preview · Article · Jul 2015 · Thorax
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    ABSTRACT: The diagnosis and staging of lung cancer is an important process that identifies treatment options and guides disease prognosis. We aimed to assess endobronchial ultrasound-guided transbronchial needle aspiration as an initial investigation technique for patients with suspected lung cancer. In this open-label, multicentre, pragmatic, randomised controlled trial, we recruited patients who had undergone a CT scan and had suspected stage I to IIIA lung cancer, from six UK centres and randomly assigned them to either endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) or conventional diagnosis and staging (CDS), for further investigation and staging. If a target node could not be accessed by EBUS-TBNA, then endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) was allowed as an alternative procedure. Randomisation was stratified according to the presence of mediastinal lymph nodes measuring 1 cm or more in the short axis and by recruiting centre. We used a telephone randomisation method with permuted blocks of four generated by a computer. Because of the nature of the intervention, masking of participants and consenting investigators was not possible. The primary endpoint was the time-to-treatment decision after completion of the diagnostic and staging investigations and analysis was by intention-to-diagnose. This trial is registered with ClinicalTrials.gov, number NCT00652769. Between June 10, 2008, and July 4, 2011, we randomly allocated 133 patients to treatment: 66 to EBUS-TBNA and 67 to CDS (one later withdrew consent). Two patients from the EBUS-TBNA group underwent EUS-FNA. The median time to treatment decision was shorter with EBUS-TBNA (14 days; 95% CI 14-15) than with CDS (29 days; 23-35) resulting in a hazard ratio of 1·98, (1·39-2·82, p<0·0001). One patient in each group had a pneumothorax from a CT-guided biopsy sample; the patient from the CDS group needed intercostal drainage and was admitted to hospital. Transbronchial needle aspiration guided by endobronchial ultrasound should be considered as the initial investigation for patients with suspected lung cancer, because it reduces the time to treatment decision compared with conventional diagnosis and staging techniques. UK Medical Research Council. Copyright © 2015 Navani et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.
    Full-text · Article · Feb 2015 · The Lancet Respiratory Medicine
  • Chapter: Lung Cancer
    Neal Navani · Stephen G. Spiro
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    ABSTRACT: This chapter contains sections titled: Introduction Clinical Features of Lung Cancer Paraneoplastic Syndromes Risk Factors for Lung Cancer Performance Status Investigation of Lung Cancer Staging of Lung Cancer An Algorithm for the Diagnosis and Staging of Non-Small-Cell Lung Cancer Mesothelioma Summary References Further Reading
    No preview · Chapter · Apr 2013
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    Full-text · Article · Feb 2012 · Thorax
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    Stephen G Spiro

    Preview · Article · Feb 2012 · Thorax
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    Stephen G Spiro · Neal Navani
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    ABSTRACT: While low-dose CT scans have been shown to detect greater numbers of early lung cancers than conventional CXR, the first randomized trial of CT versus CXR screening in more than 50 000 subjects has shown a 20% reduction in mortality with CT. There are several other randomized trials in progress. CT scanning may be a useful technique for identifying lung cancer at an earlier stage and may reduce mortality. However, before it can be used on a wider scale, issues such as overdiagnosis bias, cost-effectiveness, false positive findings of multiple noncalcified nodules and the willingness of the relevant population to accept CT scanning need to be evaluated. There is still very little information on the cost per life-year saved as a result of CT scanning, as the data to date is very imprecise. There is no evidence that screening programs influence smoking rates despite the inclusion of cessation programs in many trials. Furthermore, if CT screening is adopted, much work is needed to persuade individuals at high risk, mostly current or former heavy smokers with some airflow obstruction, to participate in a screening program.
    Full-text · Article · Dec 2011 · Respirology
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    ABSTRACT: Earlier diagnosis of lung cancer is key to reducing mortality. New evidence suggests that smokers have negative attitudes to screening and participation in lung cancer screening trials is poor (<1 in 6 of those eligible). Understanding participation is important since uptake in screening trials is likely to predict uptake in screening programmes. A qualitative study of people accepting and declining participation in the Lung-SEARCH screening trial was conducted. Two questions were addressed: Are the screening methods offered acceptable to patients? Why do some people take part and others decline? The qualitative study used semi-structured interviews with 60 respondents from three groups: (a) trial participants providing an annual sputum sample; (b) trial participants with a sputum sample showing abnormal cytology and thus undergoing annual CT scanning and bronchoscopy; and (c) those declining trial participation. Most respondents (48/60, 80%) viewed sputum provision, CT scanning and bronchoscopy as largely acceptable. Those declining trial participation described fear of bronchoscopy, inconvenience of travelling to hospitals for screening investigations and perceived themselves as having low susceptibility to lung cancer or being too old to benefit. Patients declining participation discounted their risk from smoking and considered negative family histories and good health to be protective. Four typological behaviours emerged within those declining: 'too old to be bothered', 'worriers', 'fatalists' and 'avoiders'. Sputum provision, CT scanning and bronchoscopy are largely acceptable to those participating in a screening trial. However, the decision to participate or decline reflects a complex balance of factors including acceptability and convenience of screening methods, risk perception, altruism and self-interest. Improving practical and changing cognitive aspects of participation will be key to improving uptake of lung cancer screening.
    No preview · Article · Nov 2011 · Thorax
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    Full-text · Article · Apr 2011 · Respirology
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    ABSTRACT: Lung cancer has the highest mortality of all cancers in the UK and, as such, constitutes a major public health problem. Lung-SEARCH is a UK multi-centre randomised control trial to determine whether screening (annual sputum cytology and if positive, followed by annual CT scanning and bronchoscopy) of smokers with mild COPD improves the detection of lung cancer at early stages when curative treatment is feasible. Acceptability is an ethical requirement of any screening programme. In addition, maximising participation of at-risk groups is key to any successful screening programme. We conducted a qualitative study to answer two questions: Methodology A qualitative study using semi-structured face-to-face and telephone interviews involving three groups of respondents a) those giving an annual sputum sample; b) those undergoing annual bronchoscopy and CT scanning, and c) those who declined participation in the trial. We used the Framework technique to carry out a thematic analysis. Respondent validation was used to strengthen the research findings. Results 50 interviews were completed (group a: 16, group b: 11; group c: 23). Respondents felt sputum analysis and CT scanning was acceptable. Some recalled a negative experience of bronchoscopy but would not object to future bronchoscopies. The main reasons for declining the trial include travelling for CT scanning and bronchoscopy, negative experiences/perceptions of screening tests, and low perceived susceptibility of lung cancer. There were four main typological behaviours recognised within the declining group: ‘too old to be bothered’, ‘worriers’, ‘fatalists’ and ‘avoiders’. Declining patients perceived they were at low risk compared to those taking part. Risk was believed to be related to family history and current health rather than smoking. Conclusion Whilst screening methods in the Lung-SEARCH trial are largely acceptable to trial participants, strategies to increase acceptability and participation of this at-risk group should include providing tests locally, resolving anxieties concerning screening tests and addressing beliefs of those who underestimate or deny their risk of lung cancer.
    Full-text · Article · Nov 2010 · Thorax
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    Neal Navani · Stephen G Spiro

    Full-text · Article · Aug 2010 · Respirology
  • Wayomi R Perera · Stephen G Spiro
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    ABSTRACT: Small-cell lung cancer (SCLC) is the most aggressive form of lung cancer; it is characterized by a rapid tumor-doubling time and early metastasis. Although SCLC is extremely sensitive to chemotherapy, relapses are frequent and the 5-year survival is poor. Standard treatment for all stages of SCLC consists of chemotherapy with etoposide and a platinum-based agent. The addition of thoracic radiotherapy and prophylactic cranial irradiation significantly improves survival in limited-stage disease. However, their effect in elderly patients with extensive SCLC is unknown. Chronological age is an insufficiently sensitive parameter to determine which elderly patients would most benefit from treatment; a comprehensive geriatric assessment allows better tailoring of therapy. Elderly patients with good performance status and fewer comorbidities should be treated with standard SCLC treatment regimens. Clinical trials specifically designed for SCLC patients aged 70 years or older are urgently needed.
    No preview · Article · Jun 2010 · Aging Health
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    Stephen G Spiro · Michael Niederman · Wing W Yew · José M Porcel

    Full-text · Article · Mar 2010 · Respirology
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    ABSTRACT: Lung cancer remains one of the greatest medical challenges with nearly 1.5 million new cases worldwide each year and a growing tobacco epidemic in the developing world. This review summarizes briefly the current status in growing areas of clinical research. The value of screening for early disease is not yet established and trials to see if mortality can be improved as a result are in progress. Better and more accurate staging will both streamline investigation and prove cost-effective once ultrasound-guided biopsy and aspiration of mediastinal nodes become universally accepted. This, allied to the new staging classification, will improve selection of cases for surgery, intensive multimodality therapy and for adjuvant treatment postoperatively. Much still needs to be done to refine staging as within a particular stage group, the outcome shows great variation. More information is needed on the genetic make-up in some groups of tumours and not just their size; that is, more biological data on tumour growth patterns are likely to be at least as discriminating. The place of the stem cell theory of tumorigenesis is also explored in this paper. Finally, targeted therapy for advanced non-small-cell lung cancer is highlighted as a development with early promise, but still much clarification is required, before it can be considered as a universal approach in late disease.
    Full-text · Article · Jan 2010 · Respirology
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    ABSTRACT: To evaluate the impact of adjuvant cisplatin-vinorelbine in completely resected non-small cell lung cancer and identify patients likely to benefit from this regimen in the Lung Adjuvant Cisplatin Evaluation (LACE) database. The overall LACE meta-analysis showed survival benefit with cisplatin-based adjuvant chemotherapy (5-year survival benefit of 5.4%, hazard ratio [HR] 0.89, p = 0.004). Subgroup analysis for the cisplatin-vinorelbine regimen was prespecified in the LACE statistical analysis plan. Patients randomized to cisplatin-vinorelbine or observation were the largest subgroup (41%) and the most homogeneous in terms of drug doses and eligibility. The LACE-vinorelbine cohort included trials evaluating cisplatin-vinorelbine versus observation. Overall survival was the primary end point. Other studies randomizing patients to other chemotherapy or observation (LACE-other) were also evaluated. The LACE-vinorelbine cohort included 1888 patients from four studies (Adjuvant Navelbine International Trialist Association, Big Lung Trial, International Adjuvant Lung Cancer Trial, and National Cancer Institute of Canada Clinical Trials Group JBR.10). Baseline characteristics were similar to the LACE-other but had fewer patients with stage IA (2% versus 11%). Survival improvement at 5 years was 8.9% with cisplatin-vinorelbine versus observation (HR 0.80, 95% confidence interval: 0.70-0.91, p <0.001). Stage was a significant predictor for survival (test for trend, p = 0.02; benefit at 5 years: 14.7% [stage III], 11.6% [stage II], and 1.8% [stage I]). Similar benefits were seen for disease-free survival (HR 0.75 [0.67-0.85, p <0.001], stage III [HR 0.62, 0.50-0.76], stage II [HR 0.69, 0.57-0.83], and stage I [HR 0.95, 0.767-1.19]). The overall result was statistically superior to LACE-other (LACE other HR 0.95, 0.86-1.05, interaction p = 0.04). In subgroup analyses, adjuvant cisplatin-vinorelbine provides a superior survival benefit and can be recommended in completely resected stages II and III non-small cell lung cancer.
    Full-text · Article · Dec 2009 · Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer
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    ABSTRACT: Cancers rely on angiogenesis for their growth and dissemination. We hypothesized that thalidomide, an oral antiangiogenic agent, when combined with chemotherapy, and as maintenance treatment, would improve survival in patients with advanced non-small-cell lung cancer (NSCLC). Seven hundred twenty-two patients were randomly assigned to receive placebo or thalidomide capsules 100 to 200 mg daily for up to 2 years. All patients received gemcitabine and carboplatin every 3 weeks for up to four cycles. End points were overall survival (OS), progression-free survival (PFS), response rate, grade 3/4 toxicity, and quality of life (QoL). The median OS rates were 8.9 months (placebo) and 8.5 months (thalidomide). The hazard ratio (HR) was 1.13 (95% CI, 0.97 to 1.32; P = .12). The 2-year survival rate was 16% and 12% in the placebo and thalidomide arms, respectively. The PFS results were consistent with those for OS. The risk of having a thrombotic event was increased by 74% in the thalidomide group: HR of 1.74 (95% CI, 1.20 to 2.52; P = .003). There were no differences in hematologic toxicities, but a slight excess of rash and neuropathy in the thalidomide group. QoL scores were similar but thalidomide was associated with less insomnia, and more constipation and peripheral neuropathy. In a retrospective analysis, patients with nonsquamous histology in the thalidomide group had a poorer survival: 2-year risk difference of 10% (95% CI, 4% to 16%; P < .001). In this large trial of patients with NSCLC, thalidomide in combination with chemotherapy did not improve survival overall, but increased the risk of thrombotic events. Unexpectedly, survival was significantly worse in patients with nonsquamous histology.
    Full-text · Article · Sep 2009 · Journal of Clinical Oncology
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    ABSTRACT: Cancer cells rely on angiogenesis for growth and dissemination, and small cell lung cancer (SCLC) is a highly angiogenic tumor. We evaluated thalidomide, an anti-angiogenic agent, when combined with chemotherapy and as maintenance treatment. A total of 724 patients (51% with limited and 49% with extensive disease) were randomly assigned to receive placebo or thalidomide capsules, 100-200 mg daily for up to 2 years. All patients received etoposide and carboplatin every 3 weeks for up to six cycles. Endpoints were overall survival, progression-free survival, tumor response rate, toxicity, and quality of life (QoL). Hazard ratios (HRs) for comparing thalidomide against placebo were estimated using Cox regression modeling. Statistical tests were two-sided. The median overall survival was 10.5 months (placebo) and 10.1 months (thalidomide) (HR for death = 1.09, 95% confidence interval [CI] = 0.93 to 1.27; P = .28). Among patients with limited-stage disease, there was no evidence of a survival difference (HR for death = 0.91, 95% CI = 0.73 to 1.15), but among patients with extensive disease, survival was worse in the thalidomide group (HR for death = 1.36, 95% CI = 1.10 to 1.68). Progression-free survival rates were also similar in the two groups (HR = 1.07, 95% CI = 0.92 to 1.24). Thalidomide was associated with an increased risk of having a thrombotic event, mainly pulmonary embolus and deep vein thrombosis (19% thalidomide vs 10% placebo; HR = 2.13, 95% CI = 1.41 to 3.20; P < .001). There were no statistically significant differences between treatments in hematological and nonhematological toxic effects, except more patients in the thalidomide group had rash, constipation, or neuropathy. Overall, QoL scores were similar in the two treatment groups, but thalidomide was associated with less insomnia and diarrhea and more constipation and peripheral neuropathy. In this large randomized trial, thalidomide in combination with chemotherapy did not improve survival of patients with SCLC but was associated with an increased risk of thrombotic events.
    Full-text · Article · Aug 2009 · Journal of the National Cancer Institute
  • Neal Navani · Stephen G Spiro · Sam M Janes

    No preview · Article · Jul 2009 · Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer
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    Neal Navani · Stephen G Spiro · Sam M Janes
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    ABSTRACT: Mediastinal staging of non-small-cell lung cancer (NSCLC) is of paramount importance. It distinguishes operable from inoperable disease, guides prognosis and allows accurate comparison of outcomes in clinical trials. Noninvasive imaging modalities for mediastinal staging include CT, PET and integrated PET-CT. Mediastinoscopy is considered the current gold standard; however, each of these techniques has limitations in sensitivity or specificity. These inadequacies mean that 10% of operations performed with curative intent in patients with NSCLC are futile, owing to inaccurate locoregional lymph-node staging. Endoscopic and endobronchial ultrasound-guided mediastinal lymph-node aspiration are important and promising innovative techniques with reported sensitivities and specificities higher than standard investigations. The role of these techniques in mediastinal lymph-node staging is evolving rapidly and early data suggest that they may diminish the need for invasive surgical staging of the mediastinum. Furthermore, these are outpatient procedures that do not require general anesthesia and may be combined safely in the same sitting, for optimal accuracy of mediastinal staging. We propose a new algorithm for the diagnosis and staging of NSCLC, based on the current evidence, which incorporates endoscopic and endobronchial ultrasound as a first investigation after CT in patients with intrathoracic disease.
    Full-text · Article · Jun 2009 · Nature Reviews Clinical Oncology
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    M Polkey · T Howes · G Burns · S G Spiro

    Preview · Article · Dec 2008 · European Respiratory Journal
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    ABSTRACT: The combination of cisplatin and etoposide (PE) has been a standard treatment for patients with poor-prognosis small cell lung cancer (SCLC). This non-inferiority design trial aimed to determine whether the combination of gemcitabine and carboplatin (GC) results in similar survival but is less toxic with better quality of life. Previously untreated patients with SCLC with extensive disease or limited stage with poor prognostic factors were randomly assigned to six 3-weekly cycles of GC or PE. 241 patients (121 GC, 120 PE) were recruited, of which 216 (90%) had died. There was no difference in overall survival (HR 1.01, 95% CI 0.77 to 1.32). Median survival with GC and PE was 8.0 and 8.1 months, respectively. Median progression-free survival was 5.9 months with GC and 6.3 months with PE. Grade 3 or 4 myelosuppressions were more frequent with GC (anaemia: 14% GC vs 2% PE; leucopenia: 32% GC vs 13% PE; thrombocytopenia: 22% GC vs 4% PE), but these were not associated with increased hospital admissions, infections or fatalities. Grade 2-3 alopecia (68% PE vs 17% GC) and nausea (43% PE vs 26% GC) were more frequent with PE. Patients given GC received more chemotherapy as outpatients (89% GC vs 66% PE of treatment cycles). In QoL questionnaires, more patients receiving PE reported being upset by hair loss (p = 0.004) and impaired cognitive functioning (p = 0.04). GC is as effective as PE in terms of overall survival and progression-free survival and has a toxicity profile more acceptable to patients. Trial registration number: ISRCTN 39679215.
    No preview · Article · Oct 2008 · Thorax

Publication Stats

6k Citations
1,264.54 Total Impact Points


  • 1994-2015
    • Royal Brompton and Harefield NHS Foundation Trust
      • Respiratory Medicine
      Harefield, England, United Kingdom
  • 2010
    • University Hospitals Birmingham NHS Foundation Trust
      Birmingham, England, United Kingdom
    • Cancer Research UK
      Londinium, England, United Kingdom
  • 1992-2008
    • Middlesex Hospital
      मिडलटाउन, Connecticut, United States
  • 1989-2008
    • University College London Hospitals NHS Foundation Trust
      • Department of Thoracic Medicine
      Londinium, England, United Kingdom
  • 2007
    • University of Southampton
      Southampton, England, United Kingdom
    • The University of Sheffield
      Sheffield, England, United Kingdom
  • 1982-2006
    • University of Birmingham
      Birmingham, England, United Kingdom
  • 2005
    • Medical University of South Carolina
      Charleston, South Carolina, United States
  • 2004
    • Medical Research Council (UK)
      Londinium, England, United Kingdom
  • 1991-2003
    • University College London
      • Department of Oncology
      Londinium, England, United Kingdom
  • 1999
    • Queen Elizabeth Hospital Birmingham
      Birmingham, England, United Kingdom
  • 1985
    • Liverpool Heart And Chest Hospital
      Liverpool, England, United Kingdom